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EP2701536A1 - Edible brown algae extract with a low iodine content - Google Patents

Edible brown algae extract with a low iodine content

Info

Publication number
EP2701536A1
EP2701536A1 EP12724684.1A EP12724684A EP2701536A1 EP 2701536 A1 EP2701536 A1 EP 2701536A1 EP 12724684 A EP12724684 A EP 12724684A EP 2701536 A1 EP2701536 A1 EP 2701536A1
Authority
EP
European Patent Office
Prior art keywords
extract
algae
algae extract
polyphenols
composition according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12724684.1A
Other languages
German (de)
French (fr)
Inventor
Guy POTIER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Algues et Mer SAS
Original Assignee
Algues et Mer SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Algues et Mer SAS filed Critical Algues et Mer SAS
Publication of EP2701536A1 publication Critical patent/EP2701536A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L17/00—Food-from-the-sea products; Fish products; Fish meal; Fish-egg substitutes; Preparation or treatment thereof
    • A23L17/60—Edible seaweed
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction

Definitions

  • the present invention generally relates to an extract of brown algae, especially food and its preparation process, this extract having a very low iodine content, a high content of polyphenols (or polyphenol compounds) and high levels of alginates, polysaccharides and minerals.
  • the present invention also relates to an oral absorption composition comprising such an extract.
  • the enriched human being seeks, whatever his culture, greater comfort (in the sense of a physically less demanding life) and a more varied and richer diet (especially increased consumption of meat or more sophisticated manufactured products).
  • the conjunction of these two phenomena favors the development of a set of risk factors affecting his health.
  • the human being decreases his energy consumption, but by feeding in a profusion and in a richer way, he consumes much more than his nutritional needs. This results in the appearance of a syndrome, which is described as metabolic.
  • metabolic syndrome in the sense of the present invention a set of metabolic disturbances, which although not falling within the strict definition of the disease, strongly predisposes the development and progression of true chronic diseases such as hypertension , arteriosclerosis, or diabetes.
  • a pre-diabetic is six times more likely to develop diabetes than a normal individual.
  • medical care does not occur more often than when the disease is declared.
  • Hygiene and dietary rules are then in place (more balanced meals and maintenance of physical activity) but are insufficient at this stage of the disease, which makes it necessary to use drugs (eg cholesterol-lowering drugs, antidiabetic drugs. ..).
  • Certain food products have been specifically developed to limit the development of these pathologies. These include products based on polyunsaturated fatty acids or fat adsorbers, but which are not always of real interest in the long term. Indeed, the endogenous component of these pathologies is preponderant (it is estimated at 20% the influence of dietary intakes on hypercholesterolemia).
  • the present invention therefore relates to the manufacture of food products (extracts and oral absorption compositions comprising these extracts) for the management of individuals with metabolic syndrome, and in particular pre-diabetics.
  • oral absorption composition means a product obtained by transformation of a food which is ingested in addition to the diet, around the meals, this product having only one strictly digestive action (no absorption is necessary for the digestive activity of the product and the action is done in the food bowl).
  • brown algae food extracts One known solution for the sustainable and effective management of individuals with metabolic syndrome or pre-diabetic individuals is the use of brown algae food extracts. Indeed, the inhibitory power of brown algae extracts, known to be rich in phlorotannins, on certain enzymes present in the digestive system has already been demonstrated in several publications [1] to [3] and few other food plants have such activity. These enzymes degrade complex nutrients into assimilable nutrients (especially sugars) and are therefore one of the important players influencing postprandial blood levels. By inhibiting the activity of these enzymes, the nutrients in the food bolus are more slowly digested and absorbed when taking a meal. The glycemic, insulinemic and triglyceric responses are diminished.
  • the brown algae extracts help to reduce the negative impact of excessive food intake compared to the needs, while providing certain elements necessary for the organism such as:
  • alginates which form a calcium gel in the stomach, contributing to the enzymatic inhibition activity of polyphenols (congestion of the nutrient attack sites by the enzymes) and causing a satiety effect [5];
  • fucans which inhibit the binding of Helicobacter pilori digestive walls limiting the risk of ulcers [6] or that limit enzymatic hydrolysis of starch by inhibitory effects [7].
  • the known brown algae extracts are certainly rich in phlorotannins, and thus have an inhibitory activity on certain enzymes of the digestive system.
  • they have a high iodine content, even when the extracts are subjected to deiodization. Indeed, during this desiodization, the iodine is only partially eliminated, and the residual content (300 ppm for the less rich) limits the maximum daily usable dose (500mg), and thus the clinical interest of the product.
  • the extract marketed by the applicant company itself under the brand InSea 2 ® which is a brown seaweed extract acting as an inhibitor of carbohydrate digestive enzymes, the DC-amylase and cc-glucosidase
  • the brown seaweed extract marketed by the company under the brand Bioserae Id-AIG TM the brown seaweed extract marketed by the company under the brand Bioserae Id-AIG TM
  • the white kidney bean extract marketed by Ingredia Nutritional branded Phase 2 ® or the brown algae extract manufactured by the company Diana Naturals and subject of the French patent application FR2914190.
  • the latter product is intended to combat inflammation, arthritis and allergies, it departs from the scope of the present invention.
  • Acarbose DCI (marketed by BAYER under the tradename Glucor® ND) and Orlistat DCI (marketed by the ROCHE and Glaxo SmithKline laboratories under the trade names Xenical® ND and Alli TM ND, respectively).
  • the active pharmaceutical ingredient Acarbose DCI has the disadvantage of causing flatulence, and therefore the nonobservance of the treatment
  • the pharmaceutical active ingredient Orlistat DCI presents the disadvantage of blocking the absorption of lipids, and thus to cause a very strong acceleration of the transit, and thus finally the nonobservance of the treatment.
  • the alginates are necessarily eliminated, whether by acidification (manufacture of the InSea 2 ® product), or by precipitation with calcium chloride, for example (process described in FR2914190), these additional steps entail not only the elimination of alginates (biological interest) but also additional costs;
  • iodine removal is by diafiltration (FR2914190): some of the iodine is entrained in the permeate, but also some of the minerals and dry matter; the more one wants to eliminate the iodine, the more it is necessary to diafilter, and the more the extract will be poor in molecules whose molecular mass is lower than the threshold of cutoff (InSea 2 ®: tangential ultrafiltration). In addition, certain contaminants present in the native extract and whose molecular mass is greater than the cut-off point of the membrane will concentrate in the retentate;
  • the purpose of the present invention is therefore the development of a brown algae extract with a reduced iodine content, but retaining the initial level of minerals, alginates, fucans and phlorotannins (polyphenols), such as to be as close as possible to the native extract.
  • the subject of the present invention is an algae extract, characterized in that it comprises less than 50 ppm of iodine and between 5 and 15%, and preferably between 8 and 10% of polyphenols, said percentage of polyphenols being expressed in chlorogenic acid equivalent relative to the dry weight of the extract.
  • polyphenols means the phlorotannins (or phenolic antioxidants) generally present in brown algae: these are chemical structures found very largely in the terrestrial plants and algae.
  • the special feature of algae polyphenols is that they are very large molecules whose major monomer is phloroglucinol (hence the name phlorotannins).
  • the algae extract according to the invention has an inhibitory activity on -amylase, -glucosidase and lipase.
  • the reduced iodine content of the algae extract according to the invention allows a daily intake of up to 3 g of extract according to the invention, thus conforming to the daily iodine intake recommended by the European Union. in Regulation 2006/352 fixing the maximum daily quantity of iodine at 150 mg / day (see also the corresponding French regulation as published in JORF 123 of 9 May 2006).
  • the algae extract according to the invention can advantageously be obtained from brown algae, preferably food.
  • the algae extract according to the invention may advantageously be obtained from algae (which may in particular be microalgae or macroalgae) belonging to at least one of the species selected from the species Ascophyllum sp. , Fucus sp. , Himanthalia sp. , Undaria sp. , and Laminaria sp ..
  • algae of the species Ascophyllum nodosum are preferably used.
  • the algae extract according to the invention may contain between 5 and 9% of alginates, percentage expressed as glucuronic acid equivalent relative to the dry weight of the extract.
  • alginates in the algae extract according to the invention allows the formation of a calcium gel which contributes to the enzymatic inhibition of phlorotannins and causes an effect of satiety.
  • alginates also commonly used in the treatment of gastroesophageal reflux esophageal ⁇ , would, through their power chelator, detoxify the body.
  • the algae extract according to the invention may also advantageously contain the majority of minerals (except iodine) contained in said algae before their transformation, and more particularly calcium, magnesium, potassium and phosphorus.
  • the presence of these minerals is essential to the proper functioning of the body of the human being (multiple actions).
  • the algae extract according to the invention may also advantageously comprise fucans, the properties of which are numerous and affect many areas (prevention of gastric ulcers, relief of stomach disorders, etc.). Fucans in particular exhibit inhibitory effects on the enzymatic hydrolysis of starch.
  • the present invention also relates to an oral absorption composition comprising an extract of algae according to the invention.
  • the oral absorption composition according to the invention is vehicle-free, the algae extract being incorporated into said composition without any addition.
  • the oral absorption composition according to the invention, it comprises an orally acceptable carrier present in said composition in a proportion of 0.5 by weight relative to the total weight of said composition.
  • compositions according to the invention may be in any ingestible oral dosage form, and especially in the form of capsules, lozenges, tablets, ampoules, capsules, herbal teas, oral solutions or suspensions, and powders. , flakes or granules.
  • the present invention further relates to a process for preparing an algae extract according to the invention, which comprises the following steps:
  • said method being characterized in that it comprises between the step of purifying the liquid phase and the step of drying said aqueous extract, a specific deiodification step of said purified aqueous extract which is carried out by passing on a resin exchange resin. ions.
  • the process according to the invention makes it possible, without using an organic solvent, to eliminate colloids such as alginates, obtaining a brown algae extract with a decrease in the iodine content (equal to or less than 50 ppm) which is more important than with a method of the prior art, while having a standardized polyphenol content.
  • the extract thus obtained is closer to the native extract (no loss of alginates and fucans, no loss of inhibitory activity, little loss of minerals essential substances such as calcium, potassium, magnesium and phosphorus).
  • the drying step may advantageously be carried out by atomization, lyophilization, vacuum oven or fluidized bed.
  • the drying is carried out by atomization.
  • the drying step is preceded by a step of concentration and / or standardization of said aqueous extract by adding soluble dietary fiber (in particular wheat, corn, etc.). to obtain a polyphenol content of between 5 and 15% and preferably between 8 and 10%.
  • soluble dietary fiber in particular wheat, corn, etc.
  • standardization means a step intended to adjust the polyphenol content in the extract whatever the nature or origin of the algae used to obtain the extract.
  • soluble dietary fibers examples include the soluble dietary fibers marketed by Roquette under the trademark Nutriose®.
  • the subject of the present invention is also the use of the composition according to the invention for the management of weight, the management of the metabolic syndrome, the glycemic regulation (prediabetes), the limitation of overweight, the lipidemic regulation (cholesterolemia high or subnormal), minor dyspeptic disorders, digestive acidity or mineral supplementation in humans or animals.
  • the disease is not yet declared.
  • the present invention also relates to an oral absorption composition comprising an algae extract according to the invention for its use as a medicament.
  • composition according to the invention can be used as a medicament in the treatment of diabetes, hypercholesterolemia, arterial hypertension, stroke, cardiovascular diseases, obesity, dyspepsia (digestive disorders), gastroesophageal reflux disease (GERD), gastric ulcers and mineral deficiencies in humans or animals.
  • diabetes hypercholesterolemia
  • arterial hypertension stroke
  • cardiovascular diseases obesity
  • dyspepsia digestive disorders
  • gastroesophageal reflux disease GABA
  • gastric ulcers gastric ulcers and mineral deficiencies in humans or animals.
  • Example 1 Preparation of a brown algae extract according to the present invention.
  • Fresh or dried brown seaweed Ascophyllum nodosum is harvested and then crushed.
  • An aqueous maceration is then carried out, the main objective of which is to extract the main constituents of the alga, namely polyphenols, fucans, alginates and minerals.
  • the extraction temperature is between 40 ° C and 95 ° C, and the extraction time is at least six hours.
  • a solid-liquid separation is carried out on a vibrating screen or centrifugal separator.
  • the aqueous extract thus obtained is then clarified so as to eliminate a maximum of microparticles in suspension and thus prevent clogging of the resin in the next step, this operation being carried out on filter press, filter plate or centrifugal decanter.
  • An iodine removal step of the extract is then carried out to reach a final content of less than 50 ppm. Removal of iodine from the aqueous extract is by passage over an ion exchange resin at room temperature (between 15 ° C and 25 ° C).
  • the extract is then concentrated under vacuum at low temperature to reach between 10 and 15% of dry matter, then it is standardized by adding soluble dietary fiber to obtain a final content of polyphenols between 8 and 10%.
  • the extracted liquid thus obtained is then spray-dried to obtain a fine brown powder rich in polyphenols.
  • Example 2 Determination of iodine, polyphenols, fucans and alginates of the extract of Example 1
  • this assay is performed by sodium thiosulfate titrimetry (ppm) according to the Codex Method of Nutrition and Dietary Foods, ESPA / CN 109/84.
  • this assay is carried out according to the FOLIN method and a content expressed in chlorogenic acid is obtained.
  • this assay is carried out according to the method of BLUMENKRANTZ and GA-HANSEN to metahydroxydiphenyl and a content expressed as glucuronic acid is obtained.
  • dosage is performed according to the DUBOIS method, the principle of which consists in determining the glucose content.
  • alginate content 5 to 9%, based on the dry matter
  • total sugar content about 30%;
  • the extract obtained in Example 1 has the following characteristics:
  • starch is incubated with an enzyme (human salivary amylase for example). This incubation leads to the digestion of starch and the production of maltose; a colored product is added and is intended to stop the enzymatic reaction and to reveal the presence of maltose;
  • an enzyme human salivary amylase for example
  • a colorimetric assay makes it possible to quantify, at a precise wavelength, the residual maltose; the addition of an "inhibitor" to the solution before incubation leads to the reduction of maltose and thus of its colorimetric dosage.
  • control solution makes it possible to calculate a percentage of inhibition.
  • Table 1 of results shows that at the level of the inhibition of digestive enzymes, the in vitro results obtained for the extracts of algae according to the invention (whatever the batch from which it is derived) are equivalent to those obtained with the algae extract of the prior art InSea 2 ® and the pharmaceutical active Glucor® ND.

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Abstract

The invention relates to a brown algae extract characterised in that it comprises less than 50 ppm of iodine and between 5 and 15 %, and preferably between 8 and 10 %, of polyphenols, said percentage of polyphenols being expressed as a chlorogenic acid equivalent in relation to the dry weight of the extract. The invention also relates to an oral absorption composition comprising such an extract, and to a method for preparing the extract according to the invention.

Description

Extrait d' algues brunes alimentaires à faible teneur en iode  Food grade brown seaweed extract with low iodine content
La présente invention concerne de manière générale un extrait d'algues brunes, notamment alimentaires et son procédé de préparation, cet extrait présentant une très faible teneur en iode, une teneur élevée en polyphénols (ou composés polyphénoliques ) et des teneurs importantes en alginates, polysaccharides et minéraux. La présente invention concerne également une composition d'absorption orale comprenant un tel extrait. The present invention generally relates to an extract of brown algae, especially food and its preparation process, this extract having a very low iodine content, a high content of polyphenols (or polyphenol compounds) and high levels of alginates, polysaccharides and minerals. The present invention also relates to an oral absorption composition comprising such an extract.
Dès qu'une société se développe économiquement, l'être humain qui s'enrichit recherche, quelle que soit sa culture, un plus grand confort (au sens d'une vie physiquement moins éprouvante) et une alimentation plus variée et plus riche (notamment par une consommation accrue en viandes ou en produits manufacturés plus sophistiqués) . La conjonction de ces deux phénomènes favorise le développement d'un ensemble de facteurs de risques nuisant à sa santé. En diminuant ses efforts physiques, l'être humain diminue sa consommation énergétique, mais en s' alimentant à profusion et de manière plus riche, il consomme bien plus que ses besoins nutritionnels . Il en résulte l'apparition d'un syndrome, que l'on qualifie de métabolique.  As soon as a society develops economically, the enriched human being seeks, whatever his culture, greater comfort (in the sense of a physically less demanding life) and a more varied and richer diet (especially increased consumption of meat or more sophisticated manufactured products). The conjunction of these two phenomena favors the development of a set of risk factors affecting his health. By decreasing its physical efforts, the human being decreases his energy consumption, but by feeding in a profusion and in a richer way, he consumes much more than his nutritional needs. This results in the appearance of a syndrome, which is described as metabolic.
Par syndrome métabolique, on entend, au sens de la présente invention un ensemble de perturbations métaboliques, qui bien que ne rentrant pas dans la définition stricte de la maladie, prédispose fortement au développement et à la progression de véritables pathologies chroniques telles que l'hypertension, l'artériosclérose, ou le diabète. Par exemple, un pré-diabétique a six fois plus de chance de développer un diabète qu'un individu normal. Or, la prise en charge médicale n' intervient le plus souvent que lorsque la maladie est déclarée. Les règles hygiéno-diététiques sont alors de mise (repas plus équilibrés et maintien d'une activité physique) mais sont insuffisantes à ce stade de la maladie, ce qui rend alors nécessaire l'utilisation de médicaments (par exemple des hypocholestérolémiants , des antidiabétiques...) . By metabolic syndrome is meant, in the sense of the present invention a set of metabolic disturbances, which although not falling within the strict definition of the disease, strongly predisposes the development and progression of true chronic diseases such as hypertension , arteriosclerosis, or diabetes. For example, a pre-diabetic is six times more likely to develop diabetes than a normal individual. However, medical care does not occur more often than when the disease is declared. Hygiene and dietary rules are then in place (more balanced meals and maintenance of physical activity) but are insufficient at this stage of the disease, which makes it necessary to use drugs (eg cholesterol-lowering drugs, antidiabetic drugs. ..).
Certains produits alimentaires ont été spécifiquement développés pour limiter le développement de ces pathologies. Il s'agit notamment de produits à base d'acides gras polyinsaturés ou d' adsorbeurs de graisses, mais qui ne présentent pas toujours d'intérêt réel à long terme. En effet, la composante endogène de ces pathologies est prépondérante (on estime à 20% l'influence des apports alimentaires sur l' hypercholestérolémie) .  Certain food products have been specifically developed to limit the development of these pathologies. These include products based on polyunsaturated fatty acids or fat adsorbers, but which are not always of real interest in the long term. Indeed, the endogenous component of these pathologies is preponderant (it is estimated at 20% the influence of dietary intakes on hypercholesterolemia).
La présente invention a donc pour objet de fabriquer des produits alimentaires (extraits et compositions d'absorption orale comportant ces extraits) permettant la prise en charge d' individus atteints de syndrome métabolique, et en particulier les pré-diabétiques.  The present invention therefore relates to the manufacture of food products (extracts and oral absorption compositions comprising these extracts) for the management of individuals with metabolic syndrome, and in particular pre-diabetics.
Par composition d'absorption orale, on entend, au sens de la présente invention, un produit obtenu par transformation d'un aliment que l'on ingère en complément de l'alimentation, autour des de repas, ce produit ne présentant qu'une action strictement digestive (aucune absorption n'étant nécessaire à l'activité digestive du produit et l'action se faisant dans le bol alimentaire) .  For the purposes of the present invention, the term "oral absorption composition" means a product obtained by transformation of a food which is ingested in addition to the diet, around the meals, this product having only one strictly digestive action (no absorption is necessary for the digestive activity of the product and the action is done in the food bowl).
Une solution connue pour la prise en charge durable et efficace d' individus atteints de syndrome métabolique ou d'individus pré-diabétiques réside dans l'utilisation d'extraits d'algues brunes alimentaires. En effet, le pouvoir inhibiteur des extraits d'algues brunes, connues pour être riches en phlorotannins , sur certaines enzymes présentes dans le système digestif a déjà été mis en évidence dans plusieurs publications [1] à [3] et peu d'autres plantes alimentaires possèdent une telle activité. Ces enzymes dégradent les nutriments complexes en nutriments assimilables (en particulier les sucres) et sont donc un des acteurs importants influençant les taux sanguins postprandiaux . En inhibant l'activité de ces enzymes, les nutriments présents dans le bol alimentaire sont plus lentement digérés et absorbés lors de la prise d'un repas. Les réponses glycémique, insulinémique et triglycérique s'en trouvent diminuées. One known solution for the sustainable and effective management of individuals with metabolic syndrome or pre-diabetic individuals is the use of brown algae food extracts. Indeed, the inhibitory power of brown algae extracts, known to be rich in phlorotannins, on certain enzymes present in the digestive system has already been demonstrated in several publications [1] to [3] and few other food plants have such activity. These enzymes degrade complex nutrients into assimilable nutrients (especially sugars) and are therefore one of the important players influencing postprandial blood levels. By inhibiting the activity of these enzymes, the nutrients in the food bolus are more slowly digested and absorbed when taking a meal. The glycemic, insulinemic and triglyceric responses are diminished.
Les extraits d' algues brunes permettent de diminuer l'impact négatif des apports alimentaires trop importants par rapport aux besoins, tout en apportant certains éléments nécessaires à l'organisme comme :  The brown algae extracts help to reduce the negative impact of excessive food intake compared to the needs, while providing certain elements necessary for the organism such as:
des minéraux (calcium, potassium, phosphore, magnésium, iode...), dont les apports sont essentiels à l'organisme [4] ;  minerals (calcium, potassium, phosphorus, magnesium, iodine ...), whose contributions are essential to the body [4];
des alginates, qui forment un gel calcique dans l'estomac contribuant à l'activité d'inhibition enzymatique des polyphénols (encombrement des sites d'attaque des nutriments par les enzymes) et provoquant un effet de satiété [5] ; et  alginates, which form a calcium gel in the stomach, contributing to the enzymatic inhibition activity of polyphenols (congestion of the nutrient attack sites by the enzymes) and causing a satiety effect [5]; and
des fucanes, qui inhibent la fixation d''Helicobacter pilori aux parois digestives limitant les risques d'ulcères [6] ou encore qui limitent l'hydrolyse enzymatique de l'amidon par des effets inhibiteurs [7] . fucans, which inhibit the binding of Helicobacter pilori digestive walls limiting the risk of ulcers [6] or that limit enzymatic hydrolysis of starch by inhibitory effects [7].
Les extraits d' algues brunes connus sont certes riches en phlorotannins , et de ce fait présentent une activité inhibitrice sur certaines enzymes du système digestif. Mais ils présentent une teneur en iode qui reste élevée, même lorsque les extraits sont soumis à un traitement de désiodisation . En effet, au cours de cette désiodisation, l'iode n'est que partiellement éliminé, et la teneur résiduelle (300 ppm pour les moins riches) limite la dose maximale quotidienne utilisable (500mg) , et donc l'intérêt clinique du produit. The known brown algae extracts are certainly rich in phlorotannins, and thus have an inhibitory activity on certain enzymes of the digestive system. However, they have a high iodine content, even when the extracts are subjected to deiodization. Indeed, during this desiodization, the iodine is only partially eliminated, and the residual content (300 ppm for the less rich) limits the maximum daily usable dose (500mg), and thus the clinical interest of the product.
Il est donc nécessaire que la teneur en iode de l'extrait soit réduite au maximum pour permettre l'utilisation de l'extrait à des doses efficaces.  It is therefore necessary that the iodine content of the extract be reduced to the maximum to allow the use of the extract in effective doses.
Parmi les extraits végétaux commercialisés actuellement, on peut notamment citer l'extrait commercialisé par la société Demanderesse elle-même sous la marque InSea2® (qui est un extrait d'algues brunes agissant en tant qu' inhibiteur des enzymes de digestion des glucides, l'cc-amylase et l' cc-glucosidase) , l'extrait d'algues brunes commercialisé par la société BIOSERAE sous la marque Id-AIG™, l'extrait de haricot blanc commercialisé par Ingredia Nutritional sous la marque Phase2®, ou encore l'extrait d'algues brunes fabriqué par la société Diana Naturals et faisant l'objet de la demande de brevet français FR2914190. Toutefois, ce dernier produit étant destiné à lutter contre l'inflammation, l'arthrite et les allergies, il s'éloigne du domaine de la présente invention . Among the plant extracts being marketed, there may be mentioned the extract marketed by the applicant company itself under the brand InSea 2 ® (which is a brown seaweed extract acting as an inhibitor of carbohydrate digestive enzymes, the DC-amylase and cc-glucosidase), the brown seaweed extract marketed by the company under the brand Bioserae Id-AIG ™, the white kidney bean extract marketed by Ingredia Nutritional branded Phase 2 ®, or the brown algae extract manufactured by the company Diana Naturals and subject of the French patent application FR2914190. However, since the latter product is intended to combat inflammation, arthritis and allergies, it departs from the scope of the present invention.
On peut également citer les principes actifs pharmaceutiques Acarbose DCI (commercialisé par BAYER sous la marque Glucor® ND) et Orlistat DCI (commercialisé par les laboratoires ROCHE et Glaxo SmithKline sous les marques Xenical® ND et Alli™ ND, respectivement) .  There may also be mentioned the active pharmaceutical ingredients Acarbose DCI (marketed by BAYER under the tradename Glucor® ND) and Orlistat DCI (marketed by the ROCHE and Glaxo SmithKline laboratories under the trade names Xenical® ND and Alli ™ ND, respectively).
Cependant, le principe actif pharmaceutique Acarbose DCI présente l'inconvénient de provoquer des flatulences, et donc l'inobservance du traitement, tandis que le principe actif pharmaceutique Orlistat DCI présente l'inconvénient de bloquer l'absorption des lipides, et donc de provoquer une accélération très forte du transit, et donc finalement l'inobservance du traitement. However, the active pharmaceutical ingredient Acarbose DCI has the disadvantage of causing flatulence, and therefore the nonobservance of the treatment, while the pharmaceutical active ingredient Orlistat DCI presents the disadvantage of blocking the absorption of lipids, and thus to cause a very strong acceleration of the transit, and thus finally the nonobservance of the treatment.
Quand il s'agit d'extrait d'algues, les méthodes utilisées pour éliminer l'iode lors de la fabrication ne sont pas sélectives : non seulement, elles obligent de passer par une étape chimique d'élimination des colloïdes (acidification pour la plupart entraînant des modifications structurales de l'extrait), mais elles éliminent également d'autres composés essentiels à l'organisme tels que les minéraux. Les principaux inconvénients de ces méthodes sont listés ci-après :  When it comes to seaweed extract, the methods used to eliminate iodine during manufacture are not selective: not only do they require a chemical step of eliminating colloids (acidification for the most part resulting in structural modifications of the extract), but they also eliminate other compounds essential to the body such as minerals. The main disadvantages of these methods are listed below:
lors d'une extraction à pH acide (procédé décrit dans FR2914190), un temps trop long, un pH faible, et une température élevée entraînent une hydrolyse des polyphénols, donc une perte d'efficacité et une modification importante des molécules « natives » ; on note également un risque de présence de solvants résiduels dans les extraits, selon la nature des solvants utilisés au cours de l'extraction (éthanol, autres solvants organiques) ;  during extraction at acidic pH (process described in FR2914190), a too long time, a low pH, and a high temperature lead to hydrolysis of the polyphenols, thus a loss of efficiency and a significant modification of the "native" molecules; there is also a risk of presence of residual solvents in the extracts, depending on the nature of the solvents used during the extraction (ethanol, other organic solvents);
afin d'éviter tout colmatage lors d'une élimination de l'iode par filtration tangentielle sur membrane, on élimine nécessairement les alginates, que ce soit par acidification (fabrication du produit InSea2®) , ou par précipitation au chlorure de calcium par exemple (procédé décrit dans FR2914190), ces étapes supplémentaires entraînent non seulement l'élimination des alginates (intérêt biologique) mais également des surcoûts ; in order to avoid any clogging during removal of iodine by tangential membrane filtration, the alginates are necessarily eliminated, whether by acidification (manufacture of the InSea 2 ® product), or by precipitation with calcium chloride, for example (process described in FR2914190), these additional steps entail not only the elimination of alginates (biological interest) but also additional costs;
l'élimination de l'iode par filtration tangentielle sur membrane se fait par diafiltration (FR2914190): une partie de l'iode est entraînée dans le perméat, mais également une partie des minéraux et de la matière sèche ; plus on veut éliminer l'iode, plus il faut diafiltrer, et plus l'extrait sera pauvre en molécules dont la masse moléculaire est inférieure au seuil de coupure (InSea2® : ultrafiltration tangentielle) . De plus, certains contaminants présents dans l'extrait natif et dont la masse moléculaire est supérieure au seuil de coupure de la membrane vont se concentrer dans le retentât ; removal of iodine by tangential membrane filtration is by diafiltration (FR2914190): some of the iodine is entrained in the permeate, but also some of the minerals and dry matter; the more one wants to eliminate the iodine, the more it is necessary to diafilter, and the more the extract will be poor in molecules whose molecular mass is lower than the threshold of cutoff (InSea 2 ®: tangential ultrafiltration). In addition, certain contaminants present in the native extract and whose molecular mass is greater than the cut-off point of the membrane will concentrate in the retentate;
lors de l'élimination de l'iode par chromatographie (FR2914190) sur résine adsorbante, l'emploi de solvant (s) organique (s) est nécessaire afin de pouvoir éluer les polyphénols. Une quantité plus ou moins minime de solvant (s) va persister après la phase de concentration, ce qui peut poser problème lors du séchage de l'extrait.  during the removal of iodine by chromatography (FR2914190) on adsorbent resin, the use of organic solvent (s) is necessary in order to be able to elute the polyphenols. A more or less minor amount of solvent (s) will persist after the concentration phase, which can be problematic when drying the extract.
Le but de la présente invention est donc la mise au point d'un extrait d'algues brunes avec une teneur en iode réduite, mais conservant le taux initial de minéraux, d'alginates, de fucanes et de phlorotannins (polyphénols), de manière à être le plus proche possible de l'extrait natif .  The purpose of the present invention is therefore the development of a brown algae extract with a reduced iodine content, but retaining the initial level of minerals, alginates, fucans and phlorotannins (polyphenols), such as to be as close as possible to the native extract.
Plus particulièrement, la présente invention a pour objet un extrait d'algues, caractérisé en ce qu'il comporte moins de 50 ppm d'iode et entre 5 et 15%, et de préférence entre 8 et 10 % de polyphénols, ledit pourcentage de polyphénols étant exprimé en équivalent acide chlorogénique par rapport au poids sec de l'extrait.  More particularly, the subject of the present invention is an algae extract, characterized in that it comprises less than 50 ppm of iodine and between 5 and 15%, and preferably between 8 and 10% of polyphenols, said percentage of polyphenols being expressed in chlorogenic acid equivalent relative to the dry weight of the extract.
Par polyphénols, on entend, au sens de la présente invention, les phlorotannins (ou antioxydants phénoliques) généralement présents dans les algues brunes : ce sont des structures chimiques retrouvées très largement dans les plantes terrestres et les algues. La particularité des polyphénols d'algues est que ce sont de très grosses molécules dont le monomère majoritaire est le phloroglucinol (d'où le nom de phlorotannins) . For the purposes of the present invention, the term "polyphenols" means the phlorotannins (or phenolic antioxidants) generally present in brown algae: these are chemical structures found very largely in the terrestrial plants and algae. The special feature of algae polyphenols is that they are very large molecules whose major monomer is phloroglucinol (hence the name phlorotannins).
L'extrait d'algues selon l'invention présente une activité inhibitrice sur -amylase, -glucosidase et lipase .  The algae extract according to the invention has an inhibitory activity on -amylase, -glucosidase and lipase.
La teneur réduite en iode de l'extrait d'algues selon l'invention permet une prise quotidienne pouvant aller jusque 3 g d'extrait selon l'invention, se conformant ainsi à l'apport d'iode journalier préconisé par l'Union Européenne dans le règlement 2006/352 fixant la quantité journalière maximale d'iode à 150 mg/jour (voir également à ce sujet la réglementation française correspondante telle que publiée dans le JORF 123 du 9 mai 2006) .  The reduced iodine content of the algae extract according to the invention allows a daily intake of up to 3 g of extract according to the invention, thus conforming to the daily iodine intake recommended by the European Union. in Regulation 2006/352 fixing the maximum daily quantity of iodine at 150 mg / day (see also the corresponding French regulation as published in JORF 123 of 9 May 2006).
L'extrait d'algues selon l'invention peut avantageusement être obtenu à partir d'algues brunes, de préférence alimentaires.  The algae extract according to the invention can advantageously be obtained from brown algae, preferably food.
L'extrait d'algues selon l'invention peut avantageusement être obtenu à partir d'algues (qui peuvent notamment être des micro-algues ou des macro-algues) appartenant à l'une au moins des espèces choisies parmi les espèces Ascophyllum sp . , Fucus sp . , Himanthalia sp . , Undaria sp . , et Laminaria sp ..  The algae extract according to the invention may advantageously be obtained from algae (which may in particular be microalgae or macroalgae) belonging to at least one of the species selected from the species Ascophyllum sp. , Fucus sp. , Himanthalia sp. , Undaria sp. , and Laminaria sp ..
Dans le cadre de la présente invention, on utilise de préférence des algues de l'espèce Ascophyllum nodosum.  In the context of the present invention, algae of the species Ascophyllum nodosum are preferably used.
De manière avantageuse, l'extrait d'algues selon l'invention peut contenir entre 5 et 9 % d'alginates, pourcentage exprimé en équivalent acide glucuronique par rapport au poids sec de l'extrait. La présence d'alginates dans l'extrait d'algues selon l'invention permet la formation d'un gel calcique qui contribue à l'inhibition enzymatique des phlorotannins et provoque un effet de satiété. En outre, la présence d'alginates, par ailleurs usuellement utilisés dans le traitement des reflux gastro¬ œsophagiens, permettrait, grâce à leur pouvoir chélateur, de détoxifier l'organisme. Advantageously, the algae extract according to the invention may contain between 5 and 9% of alginates, percentage expressed as glucuronic acid equivalent relative to the dry weight of the extract. The presence of alginates in the algae extract according to the invention allows the formation of a calcium gel which contributes to the enzymatic inhibition of phlorotannins and causes an effect of satiety. Furthermore, the presence of alginates, also commonly used in the treatment of gastroesophageal reflux esophageal ¬, would, through their power chelator, detoxify the body.
L'extrait d'algues selon l'invention peut en outre avantageusement contenir la majorité des minéraux (hormis l'iode) contenus dans lesdites algues avant leur transformation, et plus particulièrement le calcium, le magnésium, le potassium et le phosphore. La présence de ces minéraux est essentielle au bon fonctionnement de l'organisme de l'être humain (actions multiples).  The algae extract according to the invention may also advantageously contain the majority of minerals (except iodine) contained in said algae before their transformation, and more particularly calcium, magnesium, potassium and phosphorus. The presence of these minerals is essential to the proper functioning of the body of the human being (multiple actions).
Enfin, l'extrait d'algues selon l'invention peut en outre avantageusement comprendre des fucanes, dont les propriétés sont nombreuses et touchent de nombreux domaines (prévention ulcères gastriques, soulagement les troubles de l'estomac, etc.). Les fucanes présentent notamment des effets inhibiteurs sur l'hydrolyse enzymatique de l'amidon.  Finally, the algae extract according to the invention may also advantageously comprise fucans, the properties of which are numerous and affect many areas (prevention of gastric ulcers, relief of stomach disorders, etc.). Fucans in particular exhibit inhibitory effects on the enzymatic hydrolysis of starch.
La présente invention a également pour objet une composition d'absorption orale comprenant un extrait d'algues selon l'invention.  The present invention also relates to an oral absorption composition comprising an extract of algae according to the invention.
Selon un premier mode de réalisation de la composition d'absorption orale selon l'invention, celle-ci est exempte de véhicule, l'extrait d'algues étant incorporé dans ladite composition sans aucun ajout.  According to a first embodiment of the oral absorption composition according to the invention, it is vehicle-free, the algae extract being incorporated into said composition without any addition.
Selon un deuxième mode de réalisation de la composition d'absorption orale selon l'invention, celle-ci comporte un véhicule acceptable par voie orale, présent dans ladite composition à raison de 0,5 en poids par rapport au poids total de ladite composition.  According to a second embodiment of the oral absorption composition according to the invention, it comprises an orally acceptable carrier present in said composition in a proportion of 0.5 by weight relative to the total weight of said composition.
A titre d'exemples de véhicules utilisables dans les compositions selon l'invention, on peut notamment citer les produits fluidifiants ou lubrifiants utilisés pour la mise en forme galénique de l'extrait, et plus particulièrement le stéarate de magnésium. As examples of vehicles that can be used in the compositions according to the invention, mention may be made in particular of the fluidizing or lubricating products used for in galenic form of the extract, and more particularly magnesium stearate.
Les compositions selon l'invention peuvent se présenter sous toute forme galénique ingérable par voie orale, et notamment sous forme de gélules, de pastilles, de comprimés, d'ampoules, de capsules, de tisanes, de solutions ou de suspensions buvables, de poudres, de flocons ou de granulés.  The compositions according to the invention may be in any ingestible oral dosage form, and especially in the form of capsules, lozenges, tablets, ampoules, capsules, herbal teas, oral solutions or suspensions, and powders. , flakes or granules.
La présente invention a encore pour objet un procédé de préparation d'un extrait d'algues selon l'invention, qui comprend les étapes suivantes :  The present invention further relates to a process for preparing an algae extract according to the invention, which comprises the following steps:
o on effectue une extraction solide/liquide des algues séchées ou non, broyées ou non au préalable ;  a solid / liquid extraction of the dried or unshelled algae, ground or not crushed beforehand;
o on effectue une séparation de la phase liquide et de la phase solide du mélange ;  a separation of the liquid phase and the solid phase of the mixture is carried out;
o on purifie la phase liquide, pour obtenir un extrait aqueux purifié ;  o the liquid phase is purified to obtain a purified aqueous extract;
o on récupère l'extrait aqueux que l'on sèche ;  o the aqueous extract is recovered which is dried;
ledit procédé étant caractérisé en ce qu' il comporte entre l'étape de purification de la phase liquide et l'étape de séchage dudit extrait aqueux, une étape de désiodation spécifique dudit extrait aqueux purifié qui est réalisée par passage sur une résine échangeuse d'ions.  said method being characterized in that it comprises between the step of purifying the liquid phase and the step of drying said aqueous extract, a specific deiodification step of said purified aqueous extract which is carried out by passing on a resin exchange resin. ions.
Le procédé selon l'invention permet, sans utiliser de solvant organique ni éliminer des colloïdes tels que les alginates, l'obtention d'un extrait d'algues brunes avec une diminution de la teneur en iode (égale ou inférieure à 50 ppm) qui est plus importante qu'avec une méthode de l'art antérieur, tout en présentant une teneur en polyphénols standardisée.  The process according to the invention makes it possible, without using an organic solvent, to eliminate colloids such as alginates, obtaining a brown algae extract with a decrease in the iodine content (equal to or less than 50 ppm) which is more important than with a method of the prior art, while having a standardized polyphenol content.
En outre, l'extrait ainsi obtenu est plus proche de l'extrait natif (pas de perte en alginates et fucanes, pas de perte d'activité inhibitrice, peu de perte en minéraux essentiels tels que le calcium, le potassium, le magnésium et le phosphore) . In addition, the extract thus obtained is closer to the native extract (no loss of alginates and fucans, no loss of inhibitory activity, little loss of minerals essential substances such as calcium, potassium, magnesium and phosphorus).
Dans le procédé selon l'invention, l'étape de séchage peut être avantageusement réalisée par atomisation, lyophilisation, étuve sous vide ou sur lit fluidisé. De préférence le séchage est réalisé par atomisation.  In the process according to the invention, the drying step may advantageously be carried out by atomization, lyophilization, vacuum oven or fluidized bed. Preferably the drying is carried out by atomization.
Selon un mode de réalisation particulièrement avantageux du procédé selon l'invention, l'étape de séchage est précédée d'une étape de concentration et/ou de standardisation dudit extrait aqueux par ajout de fibres solubles alimentaires (notamment de blé, de mais, etc.) pour obtenir une teneur en polyphénols comprise entre 5 et 15% et de préférence entre 8 et 10%.  According to a particularly advantageous embodiment of the process according to the invention, the drying step is preceded by a step of concentration and / or standardization of said aqueous extract by adding soluble dietary fiber (in particular wheat, corn, etc.). to obtain a polyphenol content of between 5 and 15% and preferably between 8 and 10%.
Par standardisation, on entend, au sens de la présente invention, une étape visant à ajuster la teneur en polyphénols dans l'extrait quelle que soit la nature ou la provenance des algues utilisées pour l'obtention de 1 ' extrait .  For the purposes of the present invention, "standardization" means a step intended to adjust the polyphenol content in the extract whatever the nature or origin of the algae used to obtain the extract.
A titre d'exemples de fibres solubles alimentaires utilisables dans le cadre de la présente invention, on peut notamment citer les fibres alimentaires solubles commercialisées par la société ROQUETTE sous la marque NUTRIOSE®.  As examples of soluble dietary fibers that may be used in the context of the present invention, mention may be made especially of the soluble dietary fibers marketed by Roquette under the trademark Nutriose®.
La présente invention a également pour objet l'utilisation de la composition selon l'invention pour la gestion du poids, la prise en charge du syndrome métabolique, la régulation glycémique (prédiabète) , la limitation de la surcharge pondérale, la régulation lipidémique (cholestérolémie élevée ou subnormale) , les troubles dyspeptiques mineurs, l'acidité digestive ou la complémentation en minéraux chez l'être humain ou animal. Dans le cadre de ces différentes utilisations, la maladie n'est pas encore déclarée. Enfin, la présente invention a encore pour objet une composition d'absorption orale comprenant un extrait d'algues selon l'invention, pour son utilisation comme médicament . The subject of the present invention is also the use of the composition according to the invention for the management of weight, the management of the metabolic syndrome, the glycemic regulation (prediabetes), the limitation of overweight, the lipidemic regulation (cholesterolemia high or subnormal), minor dyspeptic disorders, digestive acidity or mineral supplementation in humans or animals. In the context of these different uses, the disease is not yet declared. Finally, the present invention also relates to an oral absorption composition comprising an algae extract according to the invention for its use as a medicament.
Plus particulièrement, une telle composition selon l'invention peut être utilisée comme médicament dans le traitement du diabète, de l' hypercholestérolémie, l'hypertension artérielle, l'accident vasculaire cérébral (AVC) , les maladies cardio-vasculaires , l'obésité, la dyspepsie (troubles digestifs) , le reflux gastro-œsophagien (RGO) , les ulcères gastriques et les carences minérales chez l'être humain ou animal.  More particularly, such a composition according to the invention can be used as a medicament in the treatment of diabetes, hypercholesterolemia, arterial hypertension, stroke, cardiovascular diseases, obesity, dyspepsia (digestive disorders), gastroesophageal reflux disease (GERD), gastric ulcers and mineral deficiencies in humans or animals.
L'invention est illustrée à l'aide des exemples ci-après, qui ne sont pas limitatifs.  The invention is illustrated by means of the following examples, which are not limiting.
EXEMPLES EXAMPLES
Exemple 1 : préparation d'un extrait d'algues brunes selon la présente invention.  Example 1: Preparation of a brown algae extract according to the present invention.
Des algues brunes Ascophyllum nodosum fraîches ou sèches sont récoltées, puis broyées. Fresh or dried brown seaweed Ascophyllum nodosum is harvested and then crushed.
On effectue ensuite une macération aqueuse, qui a pour objectif principal d'extraire les principaux constituants de l'algue, à savoir les polyphénols, les fucanes, les alginates et les minéraux. La température d'extraction est comprise entre 40°C et 95°C, et la durée d'extraction est d'au moins six heures.  An aqueous maceration is then carried out, the main objective of which is to extract the main constituents of the alga, namely polyphenols, fucans, alginates and minerals. The extraction temperature is between 40 ° C and 95 ° C, and the extraction time is at least six hours.
Puis, afin d'épuiser le résidu solide et de récupérer l'extrait aqueux, on procède à une séparation solide- liquide sur tamis vibrant ou séparateur centrifuge.  Then, in order to exhaust the solid residue and recover the aqueous extract, a solid-liquid separation is carried out on a vibrating screen or centrifugal separator.
On procède ensuite à une clarification de l'extrait aqueux ainsi obtenu, afin d'éliminer un maximum de microparticules en suspension et ainsi éviter le colmatage de la résine à l'étape suivante, cette opération étant réalisée sur filtre-presse, sur filtre-plaque ou sur décanteur centrifuge. The aqueous extract thus obtained is then clarified so as to eliminate a maximum of microparticles in suspension and thus prevent clogging of the resin in the next step, this operation being carried out on filter press, filter plate or centrifugal decanter.
On procède ensuite à une étape d'élimination de l'iode de l'extrait pour atteindre une teneur finale inférieure à 50 ppm. L'élimination de l'iode de l'extrait aqueux se fait par passage sur une résine échangeuse d'ions, à température ambiante (entre 15°C et 25°C) .  An iodine removal step of the extract is then carried out to reach a final content of less than 50 ppm. Removal of iodine from the aqueous extract is by passage over an ion exchange resin at room temperature (between 15 ° C and 25 ° C).
L'extrait est ensuite concentré sous vide à basse température pour atteindre entre 10 et 15% de matière sèche, puis il est standardisé par ajout de fibres alimentaires solubles afin d'obtenir une teneur finale en polyphénols entre 8 et 10%.  The extract is then concentrated under vacuum at low temperature to reach between 10 and 15% of dry matter, then it is standardized by adding soluble dietary fiber to obtain a final content of polyphenols between 8 and 10%.
Le liquide extrait ainsi obtenu est ensuite séché par atomisation pour l'obtention d'une poudre fine et brune riche en polyphénols.  The extracted liquid thus obtained is then spray-dried to obtain a fine brown powder rich in polyphenols.
Exemple 2 : dosage de l'iode, des polyphénols, fucanes et alginates de l'extrait de l'exemple 1. Example 2: Determination of iodine, polyphenols, fucans and alginates of the extract of Example 1
Pour l'iode, ce dosage est effectué par titrimétrie au thiosulfate de sodium (résultat en ppm) selon la méthode du Codex sur la nutrition et les aliments diététiques, ESPA/CN 109/84. For iodine, this assay is performed by sodium thiosulfate titrimetry (ppm) according to the Codex Method of Nutrition and Dietary Foods, ESPA / CN 109/84.
Pour les polyphénols, ce dosage est effectué selon la méthode FOLIN et on obtient une teneur exprimée en acide chlorogénique .  For polyphenols, this assay is carried out according to the FOLIN method and a content expressed in chlorogenic acid is obtained.
Pour les alginates, ce dosage est effectué selon la méthode de BLUMENKRANTZ et G.A-HANSEN au métahydroxydiphényl et on obtient une teneur exprimée en acide glucuronique . Pour les sucres totaux, dosage est effectué selon la méthode DUBOIS, dont le principe consiste à déterminer la teneur en glucose. For alginates, this assay is carried out according to the method of BLUMENKRANTZ and GA-HANSEN to metahydroxydiphenyl and a content expressed as glucuronic acid is obtained. For total sugars, dosage is performed according to the DUBOIS method, the principle of which consists in determining the glucose content.
Les résultats de ces dosages sont donnés ci-dessous : - teneur en alginates : 5 à 9% rapporté à la matière sèche,  The results of these assays are given below: alginate content: 5 to 9%, based on the dry matter,
teneur en polyphénols, 8 à 10% exprimée en équivalent acide glucuronique ;  polyphenol content, 8 to 10% expressed as glucuronic acid equivalent;
teneur en sucres totaux : environ 30% ;  total sugar content: about 30%;
- teneur en iode : inférieure à 50 ppm. - iodine content: less than 50 ppm.
Exemple 3 : évaluation in vitro de l'activité inhibitrice des enzymes digestives par l'extrait de l'exemple 1. On évalue in vitro l'activité inhibitrice des enzymes digestives par des extraits d'algues de l'exemple 1, obtenus selon le procédé selon l'invention mais provenant de deux lots de fabrication différents. EXAMPLE 3 In Vitro Evaluation of the Inhibitory Activity of the Digestive Enzymes Using the Extract of Example 1. In vitro the inhibitory activity of the digestive enzymes was evaluated by extracts of algae of Example 1, obtained according to US Pat. method according to the invention but from two different manufacturing batches.
L'extrait obtenu à l'exemple 1 présente les caractéristiques suivantes :  The extract obtained in Example 1 has the following characteristics:
activité inhibitrice de l' -amylase à lg/L : >80% ; activité inhibitrice de l' -glucosidase à 0. lg/L : inhibitory activity of amylase at 1 g / L:> 80%; inhibitory activity of -glucosidase at 0. lg / L:
>80% activité inhibitrice de la lipase à 0. lg/L :> 80% inhibitory activity of the lipase at 0.lg / L:
>10% ; > 10%;
Les méthodes de détermination des activités enzymatiques sont des méthodes classiques colorimétriques . Le principe est le suivant :  Methods for determining enzymatic activities are standard colorimetric methods. The principle is as follows:
de l'amidon est incubé avec une enzyme (amylase salivaire humaine par exemple) . Cette incubation conduit à la digestion de l'amidon et la production de maltose ; un produit coloré est ajouté et a pour but de stopper la réaction enzymatique et de révéler la présence de maltose ; starch is incubated with an enzyme (human salivary amylase for example). This incubation leads to the digestion of starch and the production of maltose; a colored product is added and is intended to stop the enzymatic reaction and to reveal the presence of maltose;
un dosage colorimétrique permet de quantifier, à une longueur d'onde précise, le maltose résiduel ; l'ajout d'un « inhibiteur » a la solution avant incubation conduit à la diminution du maltose et donc de son dosage colorimétrique.  a colorimetric assay makes it possible to quantify, at a precise wavelength, the residual maltose; the addition of an "inhibitor" to the solution before incubation leads to the reduction of maltose and thus of its colorimetric dosage.
des comparaisons entre solution témoin et solution test permettent de calculer un pourcentage d' inhibition .  comparisons between control solution and test solution make it possible to calculate a percentage of inhibition.
Ces résultats sont détaillés dans le tableau 1 ci- après, qui présente également les activités inhibitrices d'un extrait d'algues brunes connu de l'art antérieur InSea2® d'une part, et d'autre part celles du principe actif pharmaceutique Acarbose DCI (dans le présent exemple, on a utilisé celui commercialisé par BAYER sous la dénomination Glucor® ND) . These results are detailed in Table 1 below, which also presents the inhibitory activities of a brown algae extract known from the prior art InSea 2 ® on the one hand, and on the other hand those of the pharmaceutical active ingredient. Acarbose DCI (in the present example, the one marketed by BAYER under the name Glucor® ND) was used.
Tableau 1 : comparaison des inhibitions de l'extrait selon l'invention avec un extrait de l'art antérieur et un actif pharmaceutique Table 1: Comparison of the inhibitions of the extract according to the invention with an extract of the prior art and a pharmaceutical active ingredient
Le tableau 1 de résultats montre qu'au niveau de l'inhibition des enzymes digestives, les résultats in vitro obtenus pour les extraits d'algues selon l'invention (quel que soit le lot dont il est issu) sont équivalents à ceux obtenus avec l'extrait d'algue de l'art antérieur InSea2® et l'actif pharmaceutique Glucor® ND. Table 1 of results shows that at the level of the inhibition of digestive enzymes, the in vitro results obtained for the extracts of algae according to the invention (whatever the batch from which it is derived) are equivalent to those obtained with the algae extract of the prior art InSea 2 ® and the pharmaceutical active Glucor® ND.
Liste des références List of references
[1] « Isolation and characteri zation of brown algal polyphenols as inhibitors of -amylase, lipase and trypsin » de Barwell, C.J, Blunden, G. Manandhar, P.D, dans Journal of Applied Phycology 1, 319-323 (1989), [1] "Isolation and characterization of brown algal polyphenols as inhibitors of -amylase, lipase and trypsin" from Barwell, C.J., Blunden, G. Manandhar, P.D., in Journal of Applied Phycology 1, 319-323 (1989),
[2] « Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum» de Zhang, J., Tiller, C, Shen, J., Wang, C, Girouard, G. S., Dennis, D., Barrow, C.J., Miao, M., Ewart, H. S., dans Can . J. Physiol. Pharmacol . , 2007, 85(11), 1116- 1123,  [2] "Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions of the seaweed Ascophyllum nodosum" of Zhang, J., Tiller, C., Shen, J., Wang, C., Girouard, GS, Dennis, D., Barrow , CJ, Miao, M., Ewart, HS, in Can. J. Physiol. Pharmacol. , 2007, 85 (11), 1116-1123,
[3] « Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent -glucosidase and -amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice » de Heo, S.J., Hwang, J.Y., Choi, J.I., Han, J.S., Kim, H.J., Jeon, Y.J., dans Eur . J. Pharmacol., 2009, 615 (1-3) , 252-256,  [3] "Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent -glucosidase and -amylase inhibitor, postprandial alleviates hyperglycemia in diabetic mice" from Heo, SJ, Hwang, JY, Choi, JI, Han, JS, Kim, HJ , Jeon, YJ, in Eur. J. Pharmacol., 2009, 615 (1-3), 252-256,
[4] « Allégations de santé fonctionnelles génériques» au titre de l'article 13, paragraphe 1 du règlement CE concernant les allégations nutritionnelles et de santé,  [4] 'Generic Functional Health Claims' under Article 13 (1) of the EC Regulation concerning nutrition and health claims,
[5] « Daily ingestion of alginate reduces energy intake in free-living subjects » de J.R. Paxman, J.C. Richardson, P.W. Dettmar, B . M . Corfe, dans Appetite, 2008, vol.51, 713- 719,  [5] "Daily ingestion of alginate reduced energy intake in free-living subjects" by J. R. Paxman, J. C. Richardson, P.W. Dettmar, B. M. Corfe, in Appetite, 2008, vol.51, 713-719,
[6] « Préventive Effects of Cladosiphon Fucoidan Against Helicobacter » de Hideyuki, dans Helicobacter, 2003, vol.8, 59-65,  [6] Hideyuki's "Preventive Effects of Cladosiphon Fucoidan Against Helicobacter", in Helicobacter, 2003, vol.8, 59-65,
[7] « Inhibitory effects of fucan sulfates on enzymatic hydrolysis of starch » de MyoungLae Cho, Jung H. Han et SangGuan You, dans LWT - Food Science and Technology, 2010, vol.44 no.4 1164-1171,  [7] Inhibitory effects of fucan sulfates on enzymatic hydrolysis of starch by MyoungLae Cho, Jung H. Han and SangGuan You, in LWT - Food Science and Technology, 2010, vol.44 no.4 1164-1171,

Claims

REVENDICATIONS
1. Extrait d'algues, caractérisé en ce qu'il comporte moins de 50 ppm d'iode et entre 5 et 15 % de polyphénols, ledit pourcentage de polyphénols étant exprimé en équivalent acide chlorogénique par rapport au poids sec de l'extrait. 1. Algae extract, characterized in that it comprises less than 50 ppm of iodine and between 5 and 15% of polyphenols, said percentage of polyphenols being expressed in chlorogenic acid equivalent relative to the dry weight of the extract.
2. Extrait d'algues selon la revendication 1, comportant entre 8 et 10 % de polyphénols, ledit pourcentage de polyphénols étant exprimé en équivalent acide chlorogénique par rapport au poids sec de l'extrait.  2. Algae extract according to claim 1, comprising between 8 and 10% of polyphenols, said percentage of polyphenols being expressed in chlorogenic acid equivalent relative to the dry weight of the extract.
3. Extrait d'algues selon la revendication 1 ou 2, caractérisé en ce que lesdites algues sont brunes.  3. Algae extract according to claim 1 or 2, characterized in that said algae are brown.
4. Extrait d'algues selon l'une quelconque des revendications 1 à 3, caractérisé en ce que lesdites algues sont alimentaires.  4. Algae extract according to any one of claims 1 to 3, characterized in that said algae are food.
5. Extrait d'algues selon l'une quelconque des revendications 1 à 4, caractérisé en ce qu'il contient entre 5 et 9 % d'alginates, ledit pourcentage d' alginates étant exprimé en équivalent acide glucuronique par rapport au poids sec de l'extrait.  5. Algae extract according to any one of claims 1 to 4, characterized in that it contains between 5 and 9% of alginates, said percentage of alginates being expressed in glucuronic acid equivalent based on the dry weight of the extract.
6. Extrait d'algues selon l'une quelconque des revendications 1 à 5, caractérisé en ce qu'il contient la majorité des minéraux hormis l'iode contenus dans lesdites algues avant leur transformation par extraction.  6. algae extract according to any one of claims 1 to 5, characterized in that it contains the majority of minerals except iodine contained in said algae before their transformation by extraction.
7. Extrait d'algues selon l'une quelconque des revendications 1 à 6, caractérisé en ce que lesdites algues appartiennent à l'une au moins des espèces choisies parmi les espèces Ascophyllum sp . , Fucus sp . , Himanthalia sp . , Undaria sp . , et Laminaria sp ..  7. algae extract according to any one of claims 1 to 6, characterized in that said algae belong to at least one species selected from Ascophyllum species sp. , Fucus sp. , Himanthalia sp. , Undaria sp. , and Laminaria sp ..
8. Composition d'absorption orale comprenant un extrait d'algues tel que défini selon l'une quelconque des revendications 1 à 7.  8. An oral absorption composition comprising an algae extract as defined in any one of claims 1 to 7.
9. Composition d'absorption orale selon la revendication 8, caractérisée en ce qu'elle est exempte de véhicule. 9. oral absorption composition according to claim 8, characterized in that it is free of vehicle.
10. Composition d'absorption orale selon la revendication 8, caractérisée en ce qu'elle comporte un véhicule acceptable par voie orale, présent dans ledit extrait à raison de 0,5% à 5 % en poids par rapport au poids total de ladite composition. 10. oral absorption composition according to claim 8, characterized in that it comprises an orally acceptable carrier present in said extract in a proportion of 0.5% to 5% by weight relative to the total weight of said composition .
11. Composition selon la revendication 10, caractérisée en ce que le véhicule est constitué par du stéarate de magnésium.  11. Composition according to claim 10, characterized in that the vehicle is constituted by magnesium stearate.
12. Composition selon l'une quelconque des revendications 8 à 11, caractérisée en ce qu'elle se présente sous forme de gélule, de pastille, de comprimé, d'ampoule, de capsule, de tisane, de solution ou de suspension buvable, de poudre, de flocons, et de granulés.  12. Composition according to any one of claims 8 to 11, characterized in that it is in the form of capsule, lozenge, tablet, ampoule, capsule, herbal tea, solution or oral suspension, powder, flakes, and granules.
13. Composition selon l'une quelconque des revendications 8 à 12, caractérisée en ce qu'elle est un complément alimentaire.  13. Composition according to any one of claims 8 to 12, characterized in that it is a dietary supplement.
14. Composition selon l'une quelconque des revendications 8 à 12, caractérisée en ce qu'elle est un aliment.  14. Composition according to any one of claims 8 to 12, characterized in that it is a food.
15. Procédé pour la préparation d'un extrait d'algues tel que défini selon l'une quelconque des revendications 1 à 7, comprenant les étapes suivantes :  15. Process for the preparation of an algae extract as defined in any one of claims 1 to 7, comprising the following steps:
o on effectue une extraction solide/liquide des algues séchées ou non, broyées ou non au préalable ; a solid / liquid extraction of the dried or unshelled algae, ground or not crushed beforehand;
o on effectue une séparation de la phase liquide et de la phase solide du mélange ; a separation of the liquid phase and the solid phase of the mixture is carried out;
o on purifie la phase liquide, pour obtenir un extrait aqueux purifié ; o the liquid phase is purified to obtain a purified aqueous extract;
o on récupère l'extrait aqueux que l'on sèche ; o the aqueous extract is recovered which is dried;
ledit procédé étant caractérisé en ce qu' il comporte entre l'étape de purification de la phase liquide et l'étape de séchage dudit extrait aqueux, une étape de désiodation spécifique dudit extrait aqueux purifié qui est réalisée par passage sur une résine échangeuse d'ions. said method being characterized in that it comprises between the step of purifying the liquid phase and the step of drying said aqueous extract, a specific deiodification step of said purified aqueous extract which is carried out by passing on a resin exchange resin. ions.
16. Procédé selon la revendication 15, caractérisé en ce que le séchage est réalisé par atomisation, lyophilisation, étuve sous vide ou sur lit fluidisé. 16. The method of claim 15, characterized in that the drying is carried out by atomization, lyophilization, vacuum oven or fluidized bed.
17. Procédé selon la revendication 15 ou 16, caractérisé en ce que le séchage est précédé d'une étape de concentration et/ou de standardisation dudit extrait aqueux par ajout de fibres alimentaires solubles pour obtenir une teneur en polyphénols comprise entre 8 et 10%.  17. The method of claim 15 or 16, characterized in that the drying is preceded by a step of concentration and / or standardization of said aqueous extract by adding soluble dietary fiber to obtain a polyphenol content of between 8 and 10% .
18. Utilisation de la composition telle que définie selon l'une quelconque des revendications 8 à 14 pour la gestion du poids, le syndrome métabolique, la régulation glycémique, la limitation de la surcharge pondérale, la régulation lipidémique, les troubles dyspeptiques mineurs, l'acidité digestive ou la complémentation en minéraux chez l'être humain ou animal .  18. Use of the composition as defined according to any one of claims 8 to 14 for weight management, metabolic syndrome, glycemic control, limitation of overweight, lipidemic regulation, minor dyspeptic disorders, l digestive acidity or mineral supplementation in humans or animals.
19. Composition d'absorption orale comprenant un extrait d'algues tel que défini selon l'une quelconque des revendications 1 à 7 pour son utilisation comme médicament.  19. An oral absorption composition comprising an algae extract as defined in any one of claims 1 to 7 for use as a medicament.
20. Composition selon la revendication 19 pour son utilisation comme médicament dans le traitement du diabète, de l' hypercholestérolémie, l'hypertension artérielle, l'accident vasculaire cérébral (AVC) , les maladies cardio-vasculaires , l'obésité, la dyspepsie, le reflux gastro-œsophagien (RGO) , les ulcères gastriques et les carences minérales chez l'être humain ou animal .  20. Composition according to claim 19 for its use as a medicament for the treatment of diabetes, hypercholesterolemia, arterial hypertension, stroke, cardiovascular diseases, obesity, dyspepsia, gastroesophageal reflux disease (GERD), gastric ulcers and mineral deficiencies in humans or animals.
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