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    • 专利摘要:
    The subject of the invention is a composition comprising a mixture consisting of at least one extract of Chrysanthellum indicum, and at least two products chosen from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine. This composition is particularly useful as a nutrition product or health product to prevent and / or fight against disorders of carbohydrate metabolism and / or lipid in humans or animals.
    公开号:FR3027228A1
    申请号:FR1460064
    申请日:2014-10-20
    公开日:2016-04-22
    发明作者:Sebastien Peltier；Pascal Sirvent；Thierry Maugard
    申请人:LA ROCHELLE, University of；Valbiotis；Centre National de la Recherche Scientifique CNRS；UNIVERSITE de la ROCHELLE；Universite Blaise Pascal Clermont Ferrand II；
    IPC主号:
    专利说明:

    [0001] The present invention relates to the prevention and treatment of imbalances in carbohydrate and / or lipid metabolism in humans or animals, in particular the treatment of carbohydrate and / or lipid metabolism. Type 2 diabetes. Type 2 diabetes, the most common form of diabetes, is a chronic, progressive metabolic disease. It is characterized by chronic hyperglycemia, that is to say, an abnormally high sugar concentration in the blood, and an intolerance to carbohydrates. The main cause of this chronic hyperglycemic condition is insulin resistance and inadequate secretion in response to a given metabolic state, but other factors may be involved. To combat type 2 diabetes, it is mainly necessary to reduce blood glucose levels and reduce glycated hemoglobin (HbAlc) to a level of less than or equal to 6.5%. The treatment of type 2 diabetes consists first of all in a lifestyle modification or lifestyle and dietary measures (MHD: diet, tobacco, physical and sports activities). If MHDs are not enough, then therapeutic antidiabetic agents, usually metformin, should be used. However, metformin has many medical contraindications, such as chronic renal failure, acidosis, hypoxia, dehydration, and so on. Other therapeutic agents have been developed, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, thiazolidinediones (TZDs), or sodium inhibitors. glucose co-transporter-2 (SGLT2). However, the right therapeutic combination is complex because it requires the consideration of a large number of factors such as contraindications and adverse effects, which affect the quality of life of patients and therefore their adherence to medical treatment. MHD is very rarely followed by patients, it requires very quickly to establish a therapeutic treatment with all the adverse effects and contraindications related to these molecules, and there is no solution today adapted to the management of type 2 diabetic patients between HDM and the initiation of a therapeutic treatment. In addition, patients with type 2 diabetes have a high risk of cardiovascular morbidity and mortality. It is therefore also necessary to deal with traditional cardiovascular risk factors such as the control of circulating lipids and blood pressure. This need currently induces the taking of several drugs of different therapeutic classes simultaneously. For the control of circulating lipids, the objective is to reduce the concentration of serum cholesterol by targeting mainly the inhibition of cholesterol biosynthesis (inhibition of 3-hydroxy-3-methyl-Glutaryl-Coenzyme A or HMG-CoA reductase ). Inhibitors of HMG-CoA reductase, which are mainly statins, can have significant side effects such as myopathy with symptoms such as myalgia, fatigue and muscle stiffness and cramps.
    [0002] The objective of the invention is to overcome the various disadvantages of current treatments, by proposing a composition capable of preventing and / or combating disregulations of carbohydrate and lipid metabolism, intended to be used as a nutritional product, in particular a dietary supplement, or health product during the introduction of HDMs in order to limit the use of current antidiabetic drugs.
    [0003] The use of dietary supplements in the prevention of type 2 diabetes and in support of a lifestyle modification has already been considered, but no dietary supplement is satisfactory in terms of efficacy and none have benefited to date. a favorable opinion from the European Commission for a health claim relating to blood glucose levels pursuant to Regulation (EC) No 1924/2006.
    [0004] To meet its purpose, the invention provides a composition comprising a mixture consisting of at least one extract of Chrysanthellum indicum, and at least two products selected from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine. Extracts of Chrysanthellum indicum, extracts of Cynara scolymus, extracts of Vaccinium myrtillus or piperine have already been described and some have been used in nutrition products, but unexpectedly the combination of at least one extract of Chrysanthellum indicum , with at least two products selected from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine, leads to surprising results both on carbohydrate metabolism and on lipid metabolism in humans or animals. The invention therefore also relates to a composition comprising a mixture consisting of at least one extract of Chrysonthellum indicum, and at least two products chosen from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine, for its use as a nutritional product. or health product to prevent and / or fight against disorders of carbohydrate and lipid metabolism in humans or animals. Advantageously, the composition according to the invention has a hypoglycemic effect and makes it possible to improve the tolerance to ingested carbohydrates in the prevention or treatment of cardio-metabolic diseases, in particular of type 2 diabetes, but it is also capable of acting other cardiovascular risk factors such as dyslipidemia or blood pressure. In particular, it is able to regulate the level of circulating lipids. In addition, this hypoglycemic and hypocholesterolemic composition has no or few side effects compared to those observed with existing treatments. Other features and advantages will become apparent from the detailed description of the invention which follows. The invention therefore relates to a composition comprising a mixture consisting of: at least one extract of Chrysonthellum indicum, and at least two products selected from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine. By "X" plant extract in the sense of the invention is meant a set of molecules obtained from the plant "X" by any suitable method. In particular, mention may be made of aqueous extracts (obtained with an aqueous solvent), alcoholic extracts (obtained with the aid of an alcoholic solvent) or using an organic solvent. By aqueous solvent is meant any solvent constituted totally or by water. We can thus mention water itself, hydro-alcoholic solvents in any proportion or solvents consisting of water and a compound such as glycerin or propylene glycol in any proportion. Among the alcoholic solvents, mention may be made especially of ethanol.
    [0005] The extracts can be obtained by any suitable process, for example by a process comprising the following steps: solid / liquid extraction - separation / pressing - filtration evaporation drying - optionally incorporation of additives - homogenization - conditioning. The Chrysanthellum indicum extract is preferably an entire plant extract or aerial parts.
    [0006] It may be in particular a hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H2O or microwave. The plant / extract ratio is preferably between 1/1 to 100/1, in particular between 1/1 and 25/1. The Cynara scolymus extract is preferably an extract of leaves or roots.
    [0007] It may be in particular a hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H2O or microwave. The plant / extract ratio is preferably between 1/1 to 100/1, in particular between 1/1 and 30/1. Preferably, the extract comprises at least 0.01% of chlorogenic acid by weight relative to the total weight of dry matter of the extract, in particular at least 0.5%. The extract of Vaccinium myrtillus is preferably an extract of fruits or leaves. It may be in particular a hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H2O or microwave. The plant / extract ratio is preferably between 1/1 to 200/1, in particular between 1/1 and 60/1. Preferably, the extract comprises at least 0.1% of anthocyanins by weight relative to the total weight of dry matter of the extract, in particular at least 1%. The piperine may be contained in a Piper extract or may be a synthetic piperine. The topological formula for piperine is as follows: ## STR2 ## If the piperine is contained in a Piper extract, the mixture of the composition is invention comprises said extract. The Piper extract is preferably an extract of Piper nigrum, Piper oduncum and / or Piper longum. The Piper extract is preferably an extract of fruits or leaves.
    [0008] It may be in particular a hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H2O or microwave. The plant / extract ratio is preferably between 1/1 and 10000/1, in particular between 1/1 and 45/1. The extract preferably comprises at least 1% of piperine by weight relative to the total weight of the extract. According to a preferred embodiment, the mixture contained in the composition according to the invention consists of at least one extract of Chrysanthellum indicum, at least one Cynara scolymus extract, at least one extract of Vaccinium myrtillus and piperine. Preferably, the ratio extract of Chrysanthellum indicum / extract of Cynara scolymus / extract of Vaccinium myrtillus / piperine is between 0.01 / 0.01 / 0.01 / 0.0001 and 10/10/10/10. The mixture according to the invention is obtained by any method known to those skilled in the art. It can be obtained by simple mixing of the constituents. In addition to the mixture, the composition according to the invention may contain other products, molecules, extracts, active principles, excipients, etc. It may be for example: vitamins and minerals: for example vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc and chromium; plant extracts: for example Cinnamomum verum extract, Trigonella foenum-graecum L extract; fungi and / or yeasts: for example red yeast rice (Monascus purpureus); active ingredients: for example viniferine, resveratrol, alphalipoic acid; coating agents: for example hypromellose, microcrystalline cellulose, stearic acid, talc, sugar, shellac, povidone, beeswax; aromas: for example natural aroma of blueberry or natural strawberry flavor; acidifiers such as malic acid; anti-caking agents: for example silicon dioxide or magnesium stearate; thickeners such as xanthan gum, colloidal silica, mono and diglyceride fatty acid wrinkles; stabilizers such as calcium phosphate; emulsifiers such as soy lecithin; fillers such as corn starch; excipients: for example microcrystalline cellulose, magnesium stearate or dicalcium phosphate. The composition according to the invention may be in any form, in particular in the form of a powder, a gel, an emulsion or in liquid form, in particular in the form of tablets, capsules, capsules, sticks, sachets, ampoules, dropper. or in injectable form. The composition according to the invention can be used as a nutrition product or a health product. By nutrition product is meant all products having a nutritional and / or physiological effect, this includes, in particular, food supplements, foods, dietary products, etc. These products are in particular administrable orally, gastric or venous. By health product, one understands all the products having a beneficial effect for the health, in prevention or treatment, that this effect is physiological or pharmacological, in particular the pharmaceutical products. These products are in particular administrable orally, gastric, venous or cutaneous. The composition according to the invention can be used to prevent and / or fight against disorders of carbohydrate and / or lipid metabolism in humans or animals.
    [0009] It is particularly adapted to prevent and / or fight against type 2 diabetes in humans or animals. Indeed, it has a hypoglycemic effect and improves tolerance to ingested carbohydrates. It can be used for the prevention or treatment of type 2 diabetes in the first intention, during the introduction of HDM, thus reversing the introduction of conventional oral antidiabetic drugs. For its use to prevent and / or fight against type 2 diabetes, the composition according to the invention is preferably in the form of a composition comprising a mixture consisting of an extract of Chrysanthellum indicum, an extract of Cynara scolymus, an extract of Vaccinium myrtillus and piperine, the ratio extract of Chrysanthellum indicum / extract of Cynara scolymus / extract of Vaccinium myrtillus / Piper extract or synthetic piperine being preferably between 0.01 / 0.01 / 0.01 / 0.0001 and 10/10/10/10 in particular between 0.01 / 0.01 / 0.01 / 0.0001 and 8/8/8/1. The composition according to the invention can also be used to act on other factors of cardiovascular risk or of the metabolic syndrome. In particular, the composition according to the invention can be used to prevent and / or fight against dyslipidemia. In particular, it has a cholesterol-lowering effect and reduces total cholesterol, LDL cholesterol, circulating triglycerides and hepatic triglycerides. It also has an inhibitory activity of HMG-CoA reductase. For its use for preventing and / or controlling dyslipidemia, the composition according to the invention is preferably in the form of a composition comprising a mixture consisting of an extract of Chrysanthellum indicum, an extract of Cynara scolymus of an extract of Vaccinium myrtillus and optionally of piperine, the ratio of extract of Chrysanthellum indicum / Cynara scolymus extract / extract of Vaccinium myrtillus / Piper extract or synthetic piperine being preferably between 0.01 / 0.01 / 0, 01 / 0.0001 and 10/10/10/10 in particular between 0.01 / 0.01 / 0.01 / 0.0001 and 8/6/5/1. Finally, the composition according to the invention can be used specifically to prevent or fight against blood pressure problems.
    [0010] The invention is now illustrated by examples of extracts and compositions, as well as by test results demonstrating the effectiveness of the composition according to the invention, these examples and tests being not limiting. EXAMPLES Example 1 Example of Dry Extract of Chrysanthellum indicum The aerial parts of the plant, fresh or dry, are subjected to mechanical grinding until a coarse powder is obtained. This powder is then subjected to a maceration step for 10 to 24 hours at room temperature in a 70/10 water / ethanol mixture, and the resulting mixture is then subjected to continuous leaching at 50 ° C. in a percolator with a 70/10 water / ethanol mixture, the ratio plant / extract being 3/1. The resulting extract is then subjected to liquid / liquid washes with a nonpolar organic solvent such as di- or tri-chlorornethane. After concentration by evaporation at low pressure at 35 ° C, a liquid is obtained which freeze-dried for 24 hours gives a beige powder soluble in a water / alcohol mixture. This powder (dry extract) can be used directly or mixed in a suitable solvent before use. EXAMPLE 2 Example of Dry Extract of Vaccinium Myrtillus Blueberry in powder form obtained from fruits of Vaccinium myrtillus is subjected to a maceration step for 10 to 24 hours at room temperature in a 30/50 water / ethanol mixture The resulting mixture is then continuously leached at 50 ° C. in a percolator with a 30/50 water / ethanol mixture, the plant / extract ratio being 10/1. The extract obtained is then subjected to liquid / liquid washes with a non-polar organic solvent such as di- or tri-chloromethane. After concentration by low pressure evaporation at 35 ° C, a liquid is obtained which lyophilized for 24 hours to give a violet powder soluble in a water / alcohol mixture. Example 3 Example of Cynara scolymus Dry Extract Powdered artichoke obtained from roots of Cynaro scolymus is subjected to a maceration step for 10 to 24 hours at room temperature in water, and then subjected to the assembly obtained leaching continuously at 50 ° C in a percolator with water, the ratio plant / extract being 2/1. The resulting extract is then subjected to liquid / liquid washes with a non-polar organic solvent such as di- or tri-chloromethane. After concentration by evaporation at low pressure at 35 ° C, a liquid is obtained which freeze-dried for 24 hours gives a beige powder soluble in water. Example 4 Example of Composition According to the Invention in Tablet Form The composition of Example 4 is in the form of tablets which can be administered orally. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 22.9% of dry extract of aerial parts of Chrysanthellum indicum, 13.7% of dry extract of Cynara scolymus leaves, 36.6% of dry extract of Vaccinium myrtillus fruit and 0.2% dry extract of Piper nigrum fruit. The composition also comprises in addition to the mixture at least vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc and chromium. It also comprises excipients, in particular microcrystalline cellulose and magnesium stearate, as well as coating agents, namely hypromellose, microcrystalline cellulose and stearic acid. The composition for 3 tablets is shown in the following Table 1. Table 1. Tablet composition example Ingredient list For 3 tablets Nutritional Reference Value for 3 tablets Vaccinium myrtillus fruit dry extract 800 mg 500 mg aerosol dry extract Chrysanthellum indicum Cynara scolymus 300 dry leaf extract mg Piper Nigrum Fruit Extract 5 mg Vitamin B1 1.1 mg 100% Vitamin B3 (Inositol Hexanicotinate) 16 mg (Nicotinic Acid) 100% Pantothenic Acid (Vitamin B5) 6 mg 100% Zinc (Bisglycinate Zinc) 5 mg 50% Chromium (chromium picolinate) 40 μg 100% Microcrystalline cellulose 500 mg Magnesium stearate 50 mg Example 5 Example of composition according to the invention in tablet form The composition of Example 5 is in the form of tablets Orally administrable. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 23.9% whole plant dry extract of Chrysanthellum indicum, 23.9% dry extract of Cynara scolymus leaves, 23.9% of dry fruit extract of Vaccinium myrtillus and 0.2% of dry fruit extract of Piper nigrum. The composition also includes vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc and chromium. As excipients, it comprises microcrystalline cellulose and dicalcium phosphate. As coating agents, it comprises talc, sugar, shellac, povidone and beeswax. The composition for 3 tablets is shown in the following Table 2. Table 2. Tablet composition example Ingredient list For 3 tablets Nutritional Reference Value for 3 tablets Vaccinium myrtillus fruit dry extract 600 mg 600 mg whole plant dry extract Chrysanthellum indicum Cynara scolymus 600 dry leaf extract mg Piper Nigrum Fruit Extract 5 mg Vitamin B1 1.1 mg 100% Vitamin B3 (Inositol Hexanicotinate) 16 mg (Nicotinic Acid) 100% Pantothenic Acid (Vitamin B5) 6 mg 100% Zinc (Bisglycinate Zinc) 5 mg 50% Chromium (chromium picolinate) 40 μg 100% Microcrystalline cellulose 600 mg Dicalcium phosphate 75 mg Example 6: Example of composition according to the invention in the form of a powder to be reconstituted in water, packaged in the form of sticks The composition of Example 6 is in the form of a powder to be reconstituted in water, packaged in the form of sticks that can be administered orally. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 36.3% whole plant dry extract of Chrysanthellum indicum, 24.2% dry extract of Cynara scolymus roots, 36.3% of dry fruit extract of Vaccinium myrtillus and 2.4% of dry fruit extract of Piper longum. The composition also includes vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc and chromium. As a flavor, it includes a natural aroma of blueberry. As an acidifier, it comprises malic acid. As anti-caking agent, it comprises silicon dioxide, as thickener, xanthan gum, and as a stabilizer, calcium phosphate. Its composition is indicated in the following Table 3.
    [0011] Table 3. Example of composition in the form of a powder to be reconstituted in water and packaged in the form of sticks List of ingredients For 3 sticks Nutritional value of reference for 3 sticks Dry extract of fruit of Vaccinium myrtillus 1500 mg Dry extract of whole plants of 1500 mg Chrysanthellum indicum Dry extract of Cynara scolymus roots 1000 mg Dry extract of Piper longum fruit 100 mg Vitamin B1 1.1 mg 100% Vitamin B3 (inositol hexanicotinate) 16 mg (nicotinic acid) 100% Pantothenic acid ( vitamin B5) 6 mg 100% Zinc (zinc bisglycinate) 5 mg 50% Chromium (chromium picolinate) 40 μg 100% Example 7: Example of composition according to the invention in the form of a powder to be reconstituted in water, packaged under stick form The composition of Example 7 is in the form of a powder to be reconstituted in water, packaged in the form of sticks that can be administered orally. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 30.8% of dry extract of aerial parts of Chrysanthellum indicum, 25.6% of dry extract of Cynara scolymus leaves, 41.0% dry extract of Vaccinium myrtillus leaves and 2.6% dry extract of Piper nigrum leaves. The composition also includes vitamin B12 and chromium. As an aroma, it includes a natural aroma of strawberry. As anti-caking agent, it comprises silicon dioxide. This composition does not include anti-caking agent and thickener. The composition of such a product is shown in the following Table 4.
    [0012] Table 4. Example of composition in the form of a powder to be reconstituted in water and packaged in the form of sticks List of ingredients For 3 sticks Nutritional value of reference for 3 sticks Dry extract of leaves of Vaccinium myrtillus 1500 mg Dry extract of aerial parts 1500 mg Chrysanthellum indicum Dry extract of Cynara scolymus leaves 1000 mg Dry extract of Piper nigrum leaves 100 mg Vitamin B3 (inositol hexanicotinate) 2.5 μg 100% Chromium (chromium picolinate) 20 μg 50% Example 8: Example of composition according to the invention in capsule form The composition of Example 8 is in the form of capsules that can be administered orally. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 31.6% of dry extract of aerial parts of Chrysonthellum indicum, 47.4% of dry extract of roots of Cynara scolymus, 15.8% of dry fruit extract of Vaccinium myrtillus and 2.6% of piperine. The composition also includes vitamin B3 and zinc. As an emulsifier, it comprises soy lecithin derived from the non-GMO die, as thickeners, colloidal silica and mono- and diglycerides of fatty acids. The capsule is a fish gelatin, with glycerin and a dye, red iron oxide.
    [0013] The composition of such a product is shown in the following Table 5. Table 5. Example of composition in capsule form List of ingredients For 2 capsules Reference Nutritional Value for 2 capsules Dry extract of Vaccinium myrtillus fruit 100 mg Dry extract of 200 mg aerial parts Chrysanthellum indicum Dry extract of Cynara scolymus 300 roots mg Piperine 15 mg Vitamin B3 8 mg (nicotinic acid) 50% Zinc (zinc gluconate) 10 ng 100% Example 9 Example of composition according to the invention in capsule form The composition of Example 9 is in the form of capsules Orally administrable. It comprises, expressed as a percentage by weight, relative to the total weight of the composition, 10.4% whole plant dry extract of Chrysonthellum indicum, 20.7% dry extract of Cynara scolymus leaves, 62.1% of dry extract of Vaccinium myrtillus leaves and 2.6% of piperine. As a bulking agent, it comprises corn starch. As anti-caking agents, it comprises silicon dioxide and magnesium stearate. The capsule is of plant origin.
    [0014] The composition of such a product is shown in the following Table 6.
    [0015] Table 6. Example of composition in capsule form Ingredient list For 1 capsule Reference Nutritional Value for 1 capsule Dry extract of leaves of Vaccinium myrtillus 300 mg Dry extract of whole plants of 50 mg Chrysanthellum indicum Dry extract of leaves of Cynara scolymus 100 Piperine 15 mg IN VIVO EVALUATION OF THE EFFICACY OF THE COMPOSITION In vivo experiments on mice were performed to demonstrate the effects of the composition according to the invention, in particular on glycemia, tolerance to carbohydrates and lipids circulating. Animal model The experiments were carried out on db / db mice. The db / db mice show a leptin receptor mutation inducing a disruption of the cellular signaling of the latter. Leptin receptors are highly expressed at the level of the hypothalamus. Mice with a mutation in these receptors can not effectively regulate their energy stores. This results in elevated insulinemia in the first days of life (10 - 14 days), and obesity from 3 to 4 weeks with an increase in blood glucose. These mice are insulin-resistant, hypertriglyceridemic, and glucose intolerant. They constitute a relevant model for the study of type 2 diabetes. Experimental protocol The experimental time is 9 weeks with a "run-in" of 1 week followed by 8 weeks of supplementation with the plant extracts and a composition X. 4 compositions X were tested: - Cl: Chrysanthellum indicum + piperine (respectively 1% and 0.1% food); C2: Cynara scolymus + piperine (respectively 1% and 0.1% food); - C3: Vaccinium myrtillus + piperine (respectively 1% and 0.1% food); - C4: Chrysanthellum indicum + Cynara scolymus + Vaccinium myrtillus + piperine (respectively 1%, 1%, 1% and 0.1%).
    [0016] The composition C4 corresponds to the composition according to the invention. Per Fed control and control has also been achieved. The tested compositions were incorporated into the animal feed.
    [0017] Experimental evaluations included: Measuring body mass; Measurement of fasting blood glucose; The evolution of blood glucose levels in an oral carbohydrate tolerance test, using starch at a rate of 3 g / kg. The evaluations were performed just before the supplementation (t = 0), in the middle of the supplementation (t = 4 weeks) and at the end of the supplementation (t = 8 weeks). The results obtained are presented in tables: Table 7 for the effect on fasting glucose after 8 weeks, Table 8 for the effect on carbohydrate tolerance after 8 weeks of supplementation, Table 9 for the effect on mass body. Table 7. Effect of compositions on fasting glucose after 8 weeks Compositions Fasting blood glucose (mg / dL, mean ± SEM) Control 500.6 ± 29.2 Per Fed control 518.2 ± 38.0 Cl 410.4 ± 33.3 C2 447.9 ± 33.8 C3 384.0 ± 39.5 C4 335.3 ± 38.0 - Control, n = 8; Per Fed control, n = 10; Cl, n = 9; C2, n = 9; C3, n = 9; C4, n = 8.
    [0018] ANOVA: p <0.01; Tukey post-hoc test: - Per Fed versus C4 control, p <0.01. The compositions all significantly induced a similar decrease in food intake. As a result, a Per Fed control group, that is, consuming the same amount of food as the animals supplemented with the compositions, was achieved. This group served as a reference group (control) in statistical analyzes.
    [0019] An ANOVA was performed initially to determine whether or not there was an inter-group difference. This test made it possible to determine that there was indeed a significant difference (p <0.01). In a second step, a Tukey Post-hoc test was carried out to identify the differences between the different groups. Only one significant difference (p <0.01) was observed. This difference concerns the Per Fed control group versus the C4 group. Thus, only the C4 group induced a significant decrease in fasting blood glucose. This unequivocally demonstrates a synergistic effect of the C4 composition on fasting glucose. The other groups did not induce a significant decrease in fasting blood glucose. In other words, the other groups had no effect on fasting glucose. Table 8. Effect of compositions on carbohydrate tolerance after 8 weeks AUC compositions (week 8- week 0, mgxmin / dL) (mean ± SEM) Control 19 266 ± 5778 Per Fed control 20 355 ± 6554 Cl 3367 ± 3039 C2 1901 ± 3949 * C3 -2418 ± 3260 ** C4 -11 537 ± 4168 *** Control, n = 5; Per Fed control, n = 10; Cl, n = 9; C2, n = 8; C3, n = 10; C4, n = 8. AUC: "aera under the curve". ANOVA: p <0.0001. Tukey post-hoc tests: * Per Fed control versus C2, p <0.05; - Control Per Fed versus C3, p <0.01; - Control Per Fed versus C4, p <0.001. The compositions all significantly induced a similar decrease in food intake. As a result, a Per Fed control group has been realized. This group served as a reference group (control) in statistical analyzes. An ANOVA was performed initially to determine whether or not there was an inter-group difference. This test determined that there was indeed a significant difference (p <0.0001). In a second step, a Tukey Post-hoc test was carried out to identify the differences between the different groups. Although compositions C2, C3 and C4 all induced a significant improvement in carbohydrate tolerance compared to the Per Fed reference group (p <0.05, p <0.01, p <0.001 respectively), composition C4 had the most marked effect thus demonstrating greater efficiency compared to other compositions.
    [0020] Table 9. Effect of the compositions on body mass after 8 weeks. Compositions Body mass (in g, mean ± SEM) Control 39.7 ± 2.0 Per Fed control 30.6 ± 1.2 Cl 33.9 ± 2.4 C2 37.4 ± 2.2 C3 37.0 ± 2.7 C4 36.3 ± 1.7 Control, n = 14; Per Fed control, n = 10; Cl, n = 9; C2, n = 9; C3, n = 9; C4, n = 8. ANOVA: not significant.
    [0021] The compositions all significantly induced a similar decrease in food intake. As a result, a Per Fed control group has been realized. This group served as a reference group (control) in statistical analyzes. An ANOVA was performed initially to determine whether or not there was an inter-group difference. This test determined that there were no inter-group differences. Consequently, none of the compositions induced a change in body weight, so that the effects observed for the composition according to the invention are well related to the composition as such and not to an improvement which would be related to a loss of body mass.
    [0022] IN VITRO EVALUATION OF THE EFFICACY OF THE COMPOSITION In vitro experiments were also carried out to demonstrate the effects of the composition according to the invention, in particular on the activity of HMG-CoA reductase. Principle of the test for determining the inhibitory effect of the invention on the activity of HMGCoA reductase This test measures the rate of degradation of NADPH by the enzyme HMG-CoA reductase in the presence of HMG-CoA. A substance can thus be defined as inhibiting if it allows a decrease in this rate of degradation. NADPH can be quantified by an absorbance reading at 340 nm, its degradation rate is directly correlated with the observed decrease in absorbance.
    [0023] Experimental Protocol - Solubilize the sample in a 50/50 (v / v) water / ethanol mixture, or 100% ethanol, or 100% water, at a concentration of 1 mg / mL; - Apply cold (in the ice) a sonication step of 20 minutes at 100% with a frequency of 0.5; In 170 μl of the reaction buffer, mix 12 μl of the sample of the invention to a final concentration of 60 μg / ml, 211 μl of HMG-CoA reductase at a final concentration of 6 μg / ml, 4 μl. IL of NADPH at a final concentration of 0.33 mg / mL; Incubate at 37 ° C for 15 minutes; Add 12 μL of the HMG-CoA substrate to the mixture to initiate the reaction; Incubate for 15 minutes at 37 ° C., performing OD kinetics at 340 nm, thus measuring the rate of degradation of NADPH by the enzyme HMG-CoA reductase. Preferably, the test is carried out in a 96-well microplate and triplicate.
    [0024] The results are expressed as percent inhibition of HMG-CoA reductase. The calculation of this percentage of inhibition is carried out according to the equation below:% inhibition = (Slope OD control -Pente DO Ech) x 100 Slope DO control in which: ^ (Slope OD test sample corresponds to the density optical obtained for the mixture "sample + enzyme + substrate"; (Slope OD test control corresponds to the optical density obtained for the mixture "buffer + enzyme + substrate." The results obtained are shown in Table 10. Table 10. Effect of the composition on the percentage inhibition of HMG-CoA reductase Composition% inhibition C4 97,47 The composition according to the invention induces a total inhibition of HMG-CoA reductase. pathologies associated with an increase in HMG-CoA reductase especially on dyslipidemia.
    权利要求:
    Claims (20)
    [0001]
    REVENDICATIONS1. A composition comprising a mixture of at least one extract of Chrysanthellum indicum, and at least two products selected from a Cynara scolymus extract, an extract of Vaccinium myrtillus and piperine.
    [0002]
    2. Composition according to claim 1, characterized in that the mixture consists of at least one extract of Chrysanthellum indicum, an extract of Cynara scolymus, an extract of Vaccinium myrtillus and piperine.
    [0003]
    3. Composition according to one of the preceding claims, characterized in that the piperine is contained in a Piper extract.
    [0004]
    4. Composition according to claim 3, characterized in that the Piper extract is an extract of Piper nigrum, Piper oduncum and / or Piper longum.
    [0005]
    5. Composition according to one of the preceding claims, characterized in that the extract of Chrysanthellum indicum is an extract corresponding to at least one of the following characteristics: whole plant extract or aerial parts hydroalcoholic or aqueous extract or subcritical CO2 or H20 subcritical or microwave, - plant / extract ratio between 1/1 to 100/1.
    [0006]
    6. Composition according to one of the preceding claims, characterized in that the Cynara scolymus extract is an extract satisfying at least one of the following characteristics: extract of leaves or roots hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H20 or microwave, plant / extract ratio of between 1/1 to 100/1 extract comprising at least 0.01% of chlorogenic acid by weight relative to the total weight of dry matter of the extract.
    [0007]
    7. Composition according to one of the preceding claims, characterized in that the extract of Vaccinum myrtillus is an extract satisfying at least one of the following characteristics: fruit extract or leaves-extract comprising at least 0.1% of anthocyanins by weight relative to the total weight of dry matter of the extract - hydroalcoholic extract or aqueous extract or subcritical CO2 or subcritical H2O or microwave, - ratio plant / extract 1/1 to 200/1.
    [0008]
    8. Composition according to one of claims 3 to 7, characterized in that the Piper extract is an extract satisfying at least one of the following characteristics: fruit extract or leaves hydroalcoholic or aqueous extract or subcritical CO2 or subcritical H20 or microwave, plant / extract ratio of between 1/1 to 10000/1 - extract comprising at least 1% of piperine by weight relative to the total weight of dry matter of the extract.
    [0009]
    9. Composition according to claim 1 or 2, characterized in that the piperine is synthetic piperine.
    [0010]
    10. Composition according to one of claims 3 to 8, characterized in that in the mixture, the ratio extracted from Chrysonthellum indicum / Cynara scolymus extract / Vaccinium myrtillus extract / Piper extract is between 0.01 / 0, 01 / 0,01 / 0,0001 and 10/10/10/10.
    [0011]
    11. A composition according to claim 9, characterized in that in the mixture, the ratio extracted from Chrysanthellum indicum / extract of Cynara scolymus / Vaccinium myrtillus extract / synthetic piperine is between 0.01 / 0.01 / 0.01 / 0.0001 and 10/10/10/10.
    [0012]
    12. Composition according to one of the preceding claims, characterized in that it is in the form of powder, gel, emulsion, or in liquid form.
    [0013]
    13. Composition according to one of the preceding claims characterized in that it is in the form of tablets, capsules, capsules, sticks, sachets, ampoules, dropper or injectable form.
    [0014]
    14. Composition according to one of the preceding claims for its use as a nutrition product or health product to prevent and / or fight against disruption of carbohydrate metabolism and / or lipid in humans or animals.
    [0015]
    15. Composition for its use according to claim 14, as a nutrition product or health product to prevent and / or fight against type 2 diabetes in humans or animals.
    [0016]
    16. Composition for its use according to claim 15, characterized in that the piperine is contained in a Piper extract or the piperine is synthetic piperine and in that the ratio extracted from Chrysonthellum indicum / Cynara scolymus extract / extract of Vaccinium myrtillus / Piper extract or synthetic piperine is between 0.01 / 0.01 / 0.01 / 0.0001 and 8/8/8/1.
    [0017]
    17. Composition for its use according to claim 14, as a nutrition product or health product to prevent and / or fight against dyslipidemia.
    [0018]
    18. Composition for its use according to claim 17, characterized in that the piperine is contained in a Piper extract or the piperine is synthetic piperine and in that the ratio extracted from Chrysonthellum indicum / Cynara scolymus extract / extract of Vaccinium myrtillus / Piper extract or synthetic piperine is between 0.01 / 0.01 / 0.01 / 0.0001 and 8/6/5/1.
    [0019]
    19. Composition for its use according to claim 14, as product nutrition or health product to fight against the metabolic syndrome.
    [0020]
    20. A composition for use according to claim 14 as a nutrition product or health product for combating blood pressure problems.
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    同族专利:
    公开号 | 公开日
    KR20170102861A|2017-09-12|
    EP3533454A1|2019-09-04|
    IL250742A|2019-08-29|
    CA2958676A1|2016-04-28|
    CN111973660A|2020-11-24|
    SG10201807815WA|2018-10-30|
    US20190060383A1|2019-02-28|
    US20160106793A1|2016-04-21|
    IL250742D0|2017-04-30|
    JP2021059552A|2021-04-15|
    NZ729290A|2019-10-25|
    EP3332793B1|2020-03-18|
    EP3332793A1|2018-06-13|
    TR201910765T4|2019-08-21|
    RU2019121363A|2019-10-04|
    RS59259B1|2019-10-31|
    SA517380987B1|2020-07-22|
    PT3209315T|2019-07-31|
    AR102372A1|2017-02-22|
    CN106794214B|2021-06-15|
    HRP20191288T1|2019-11-01|
    CL2017000437A1|2018-03-16|
    MA40571B1|2019-08-30|
    WO2016062958A1|2016-04-28|
    SI3209315T1|2019-11-29|
    BR112017003948A2|2018-03-06|
    RU2017106059A|2018-11-22|
    EP3209315A1|2017-08-30|
    CN106794214A|2017-05-31|
    US9962420B2|2018-05-08|
    ES2737891T3|2020-01-16|
    MA44398A|2019-01-23|
    JP6882165B2|2021-06-02|
    RU2712625C2|2020-01-30|
    ZA201701418B|2018-05-30|
    EP3209315B1|2019-04-24|
    SG11201701523VA|2017-04-27|
    FR3027228B1|2016-12-09|
    LT3209315T|2019-10-25|
    PL3209315T3|2019-11-29|
    MX2017002626A|2017-10-11|
    AU2015334754B2|2021-01-28|
    RU2017106059A3|2019-04-04|
    MA40571A|2017-08-30|
    JP2017533178A|2017-11-09|
    DK3209315T3|2019-07-29|
    JP2020121973A|2020-08-13|
    US20170028004A1|2017-02-02|
    HUE045248T2|2019-12-30|
    AU2015334754A1|2017-03-09|
    US10232005B2|2019-03-19|
    US10736930B2|2020-08-11|
    CL2017002806A1|2018-05-11|
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    法律状态:
    2015-10-28| PLFP| Fee payment|Year of fee payment: 2 |
    2016-04-22| PLSC| Publication of the preliminary search report|Effective date: 20160422 |
    2016-08-26| AU| Other action affecting the ownership or exploitation of an industrial property right|Effective date: 20160722 |
    2016-10-24| PLFP| Fee payment|Year of fee payment: 3 |
    2017-10-26| PLFP| Fee payment|Year of fee payment: 4 |
    2018-04-13| TQ| Partial transmission of property|Owner name: UNIVERSITE DE LA ROCHELLE, FR Effective date: 20180309 Owner name: UNIVERSITE CLERMONT AUVERGNE, FR Effective date: 20180309 Owner name: VALBIOTIS, FR Effective date: 20180309 Owner name: CNRS, FR Effective date: 20180309 |
    2018-10-25| PLFP| Fee payment|Year of fee payment: 5 |
    2019-10-28| PLFP| Fee payment|Year of fee payment: 6 |
    2020-10-27| PLFP| Fee payment|Year of fee payment: 7 |
    2020-12-04| CD| Change of name or company name|Owner name: VALBIOTIS, FR Effective date: 20201023 Owner name: UNIVERSITE CLERMONT AUVERGNE, FR Effective date: 20201023 Owner name: LA ROCHELLE UNIVERSITE, FR Effective date: 20201023 Owner name: CNRS, FR Effective date: 20201023 |
    2021-10-27| PLFP| Fee payment|Year of fee payment: 8 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1460064A|FR3027228B1|2014-10-20|2014-10-20|COMPOSITION COMPRISING A MIXTURE OF PLANT EXTRACTS AND USE FOR ACTING ON GLUCIDIC AND / OR LIPID METABOLISM|FR1460064A| FR3027228B1|2014-10-20|2014-10-20|COMPOSITION COMPRISING A MIXTURE OF PLANT EXTRACTS AND USE FOR ACTING ON GLUCIDIC AND / OR LIPID METABOLISM|
    CN202010730803.8A| CN111973660A|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or of molecules contained in said plants and uses thereof|
    MA40571A| MA40571B1|2014-10-20|2015-10-20|Composition comprising a mixture of plant extracts or a mixture of molecules contained in these plants and use for acting on the carbohydrate and / or lipid metabolism|
    ES15801895T| ES2737891T3|2014-10-20|2015-10-20|Composition comprising a mixture of plant extracts or a mixture of molecules contained in these plants and use to act on the glycidic and / or lipid metabolism|
    ES17203260T| ES2797084T3|2014-10-20|2015-10-20|Composition comprising a mixture of plant extracts or a mixture of molecules contained in these plants and use to act on carbohydrate and / or lipid metabolism|
    PT15801895T| PT3209315T|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    RU2019121363A| RU2019121363A|2014-10-20|2015-10-20|COMPOSITION CONTAINING A MIXTURE OF PLANT EXTRACTS OR A MIXTURE OF MOLECULES CONTAINED IN THE SPECIFIED PLANTS AND APPLICATION FOR CONTROLING THE CARBOHYDRATE AND / OR LIPID METABOLISM|
    PL15801895T| PL3209315T3|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    BR112017003948-6A| BR112017003948A2|2014-10-20|2015-10-20|composition|
    MX2017002626A| MX2017002626A|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism.|
    KR1020177008665A| KR20170102861A|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    CN201580047218.5A| CN106794214B|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants|
    NZ72929015A| NZ729290A|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling carbohydrate and/or lipid metabolism|
    SI201530832T| SI3209315T1|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    RU2017106059A| RU2712625C2|2014-10-20|2015-10-20|Composition containing mixture of plant extracts or mixture of molecules contained in said plants, and use for controlling metabolism of carbohydrates and/or lipids|
    DK15801895.2T| DK3209315T3|2014-10-20|2015-10-20|A composition comprising a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and / or lipid metabolism|
    SG11201701523VA| SG11201701523VA|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    EP15801895.2A| EP3209315B1|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    EP17203260.9A| EP3332793B1|2014-10-20|2015-10-20|Composition comprising a mixture of plant extracts or a mixture of molecules contained in said plants and use to act on the carbohydrate and/or lipid metabolism|
    JP2017510671A| JP6882165B2|2014-10-20|2015-10-20|A composition containing a mixture of plant extracts, or a mixture of molecules contained in this plant, and its use for controlling glucose metabolism and / or lipid metabolism.|
    EP18200636.1A| EP3533454A1|2014-10-20|2015-10-20|Composition comprising a mixture of plant extracts or a mixture of molecules contained in said plants and use to act on the carbohydrate and/or lipid metabolism|
    HUE15801895A| HUE045248T2|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    AU2015334754A| AU2015334754B2|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    PCT/FR2015/052805| WO2016062958A1|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    LT15801895T| LT3209315T|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    US14/887,416| US9962420B2|2014-10-20|2015-10-20|Compositions and methods for treating diabetes, fatty liver, cardiopathies, insulin resistance, carbohydrate and fat metabolism|
    TR2019/10765T| TR201910765T4|2014-10-20|2015-10-20|Composition comprising a mixture of herbal extracts or a mixture of molecules present in these plants and their use to effect carbohydrate and / or lipid metabolism.|
    SG10201807815WA| SG10201807815WA|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling carbohydrate and/or lipid metabolism|
    ARP150103392A| AR102372A1|2014-10-20|2015-10-20|COMPOSITION THAT INCLUDES A MIXTURE OF VEGETABLE EXTRACTS OR A MIXTURE OF MOLECULES CONTAINED IN THESE VEGETABLES, AND ITS USE TO ACT ON GLUCIDICAL AND / OR LIPID METABOLISM|
    RSP20190945| RS59259B1|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    MA044398A| MA44398A|2014-10-20|2015-10-20|COMPOSITION CONSISTING OF A MIXTURE OF VEGETABLE EXTRACTS OR A MIXTURE OF MOLECULES CONTAINED IN THESE PLANTS AND USE TO ACT ON GLUCIDIC AND / OR LIPID METABOLISM|
    CA2958676A| CA2958676A1|2014-10-20|2015-10-20|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    US15/296,323| US10232005B2|2014-10-20|2016-10-18|Compositions and methods for controlling carbohydrate and fat metabolism|
    IL250742A| IL250742A|2014-10-20|2017-02-23|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling carbohydrate and/or lipid metabolism|
    CL2017000437A| CL2017000437A1|2014-10-20|2017-02-23|Composition that contains a mixture of plant extract or a mixture of molecules contained in said plants, and its use to control the metabolism of lipids or carbohydrates|
    ZA2017/01418A| ZA201701418B|2014-10-20|2017-02-24|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling carbohydrate and/or lipid metabolism|
    SA517380987A| SA517380987B1|2014-10-20|2017-02-27|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants|
    CL2017002806A| CL2017002806A1|2014-10-20|2017-11-07|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use to control the metabolism of carbohydrates and / or lipids .|
    US16/175,338| US10736930B2|2014-10-20|2018-10-30|Compositions and methods for controlling carbohydrate and fat metabolism|
    HRP20191288| HRP20191288T1|2014-10-20|2019-07-17|Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants, and use for controlling glucide and/or lipid metabolism|
    JP2020041359A| JP2020121973A|2014-10-20|2020-03-10|Mixture of plant extracts, or composition comprising mixture of molecules included in that plant, and use for regulating carbohydrate metabolism and/or fat metabolism|
    JP2020201638A| JP2021059552A|2014-10-20|2020-12-04|Mixture of plant extracts or composition containing mixture of molecules contained in that plant, and use for regulating carbohydrate metabolism and/or fat metabolism|
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