WO2017072219A1 - Agent nutritionnel ou therapeutique particulier comprenant un melange de raisin et de bleuet - Google Patents
Agent nutritionnel ou therapeutique particulier comprenant un melange de raisin et de bleuet Download PDFInfo
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Definitions
- ferulic acid at least 5 ppm (parts per million in the mixture) of ferulic acid, preferably at least 10 ppm.
- quercetin and / or quercetin glycosides at least 50 ppm quercetin and / or quercetin glycosides, and / or
- the agent according to the invention is therefore particularly useful especially as a medicine in humans or animals, and specifically to prevent and / or fight against pathologies associated with cognitive decline.
- FIG. 1 represents the differences in the bioavailability of polyphenols in mouse plasma, between acute administration and chronic administration of an extract of Vitis vinifera, an extract of Vaccinium angustifolium or an agent according to the invention
- FIG. 4C shows the effects of epicatechin alone on the protection of neuronal cells after acute treatment
- FIG. 5A shows the effects of ferullic acid alone, catechin alone and epicatechin alone, on the protection of neuronal cells after three cumulative treatments (cell survival);
- the subject of the invention is therefore a nutritional or therapeutic agent comprising at least one mixture of molecules obtained from Vitis vinifera and Vaccinium angustifolium, said mixture comprising:
- quercetin and / or glycosides of quercetin at least 50 ppm of quercetin and / or glycosides of quercetin, preferably at least 70 ppm of quercetin and / or glycoside, in particular between 50 ppm and
- the term “anthocyanidin” means all the anthocyanins or anthocyanins or anthocanthocyanosides, of aglycone or glycosylated form (that is to say carrying sugars).
- the terms “anthocyanidin”, “anthocyanin”, “anthocyanins” and “anthocanthocyanosides” are equivalent.
- At least X% of the mixture of catechins and epicatechins is meant.
- ppm parts per million (mg / kg) in the mixture. Unless otherwise indicated, ppm refers to a weight based on the total weight of the mixture.
- the mixture of molecules is a mixture consisting of an extract of Vitis vinifera and an extract of Vaccinium angustifol! Um.
- the mixture of molecules is a mixture consisting of an extract obtained from a mixture of Vitis vinifero and Vaccinium angustifolium.
- the mixture of molecules is a mixture consisting of:
- Vaccinium angustifolium extract within the meaning of the invention is meant at least one molecule, preferably a set of molecules, obtained from Vaccinium angustifolium.
- the raw material can be the leaves and / or the fruits, preferably the raw material is the whole of the leaves and fruits of the plant.
- extract obtained from a mixture of Vitis vinifero and Vaccinium angustifolium is meant a set of molecules obtained from a mixture of Vitis vinifero and Vaccinium angustifolium.
- the raw material of Vitis vinifero can be the leaves and / or the fruits and / or the pips and / the woods, preferentially the raw material of Vitis vinifero is the aerial part of the plant, that is to say all the leaves, fruits, skin (pedicle), seeds and wood, more preferably the skin (film) and pips.
- the raw material of Vaccinium angustifolium may be the leaves and / or the fruits, preferentially the raw material of Vaccinium angustifolium is the whole of the leaves and fruits of the plant.
- the extracts according to the invention can be obtained by any method making it possible to obtain a mixture comprising;
- Preferentially malvidin 3 glucoside is the predominant anthocyanidin with a concentration of at least 300 ppm.
- the anthocyanidins comprise at least 20%, more preferably at least 25% malvidin glycoside (percent by weight).
- the amount of solvent (30% v / v to 96% V / V) used is between 2 and 10 times the mass of material used.
- the duration of the extraction can be between 30 minutes and 24 hours and the extraction temperature between 20 * C and 80 * C.
- the raw materials used may be in dry, fresh, or frozen forms whole or crushed;
- the amount of solvent (30% v / v to 96% V / V) used is between 2 and 10 times the mass of material used.
- the duration of the extraction can be between 30 minutes and 24 hours and the extraction temperature between 20 ° C. and 80 ° C.
- the raw materials used can be in dry, fresh or frozen forms;
- the agent may be in any form suitable for nutritional or therapeutic application, preferably in powder form.
- the nutritional or therapeutic agent can be used in particular for agfr on the cognitive and executive functions in an individual or a healthy animal but also in sick subjects.
- Alzheimer's disease is the most common cause of dementia, affecting more than 24 million people worldwide. It is irreversible in our current state of knowledge, the only available treatments being purely symptomatic. In animals, these conditions can be very similar.
- cognitive dysfunction syndrome CDD is a widespread pathology characterized by spatiotemporal disorientation, a loss of elementary learning that often leads to uncleanliness, impaired sleep-wake alteration of social interactions.
- the agent according to the invention is capable of improving the cognitive and executive functions in humans or animals.
- the invention is now illustrated by means of examples and results of tests demonstrating the synergistic antioxidant effect and on the cognitive and executive functions, and the improvement of the bioavailability of the therapeutic or nutritional agent which is the subject of the present application.
- This first example of a mixture according to the invention is obtained by implementing the method as described below.
- the other part is then mixed with the extract of Vaccinium ongustifolium to form the mixture according to the invention and a maltodextrin is added to the mixture until a solution having a solids content of 3096 is obtained.
- the solution is then spray-dried with an inlet temperature of 160 ° C.
- the product obtained is a purple powder containing the polyphenols shown in Table 1.
- the polyphenols shown in this table were measured by high speed liquid chromatography. MS / MS.
- the raw materials used are:
- the product obtained is a purple powder containing the polyphenols shown in Table 2b.
- the polyphenols shown in this table were measured by UPLC-MS / MS high speed liquid chromatograph.
- Example 4 is a 400 mg capsule consisting of:
- the recommended dosage is 1 to 2 capsules per day.
- composition is obtained by mixing the constituents under the conventional conditions known to those skilled in the art.
- Example 2 The agent according to the invention of Example 2 was added to an extruded dry dog kibble complying with AFCO standards and including animal meal, fat, fiber, cereals and preservatives. antioxidants.
- the addition of the agent to the kibble has been done according to several embodiments, in particular by coating and by inclusion.
- Inclusion tests were carried out by adding the agent according to the invention (0.02%, 0.04% or 0.1%, the% being relative to the weight of the kibble) in the raw material (also called premix) before extrusion.
- Example 7 Veterinary Product
- Gelatin capsules were prepared in a standard manner, adding an agent according to the invention of Example 2 and a martodextrin (Control, Glucidexl2 lot # 421A323532, Roquette, Lestrem Cedex, France).
- Test 1 Effect on the beaodisoonibility in mice
- the objective of this test is to compare the bioavailability of the polyphenols contained in the therapeutic or nutritional agent according to the invention (mixture of Example 1) with the bioavailability of polyphenols contained in an extract of Vttis vinlferaVitis vinifera and those contained in an extract of Vaccinium angustifolium (those described in Example 1), after oral administration algae (1 day) and chronic (15 days) to mice.
- mice Seventy-two male and female 4-month-old mice were divided into two groups to perform the acute study and the chronic study separately. In each group, three subgroups of 10 were created, each subgroup receiving a different treatment: Vltis vinifera extract, Vaccinium angustifolium extract and mixture of Example 1, and a fourth subgroup of 6 treated mice. with water (control group). The treatments are administered orally by gavage. The mixture was administered at a dose of 500 mg / kg body weight, and Vitis vinifera extract and Vaccinium angustifolium extract were administered at a dose equivalent to their amount in the mixing dose.
- Plasma concentrations of phenolic metabolites after acute and chronic administration of different treatments were compared using the Weich statistical test (Unequal Variance Correction) when the data was assumed to be normally distributed, or when it was not using the Mann-Whitney test, with the G raphPad Prism 6.05 software.
- the effects of treatments on circulating phenolic metabolite concentrations and accumulated excreta concentrations were analyzed for pairwise comparison using the Welch statistical test for normal data and the otherwise Mann-Whitney test. .
- Multiple comparisons were performed using an analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis test, a test based on data in a normal distribution or not. The differences were considered significant at p ⁇ 0.05.
- Figure 2 represents the hierarchical ascending classification (CAH) of phenolic metabolites analyzed in mice before Qour 0) and after (day 15) chronic ingestion of the three treatments.
- CAH hierarchical ascending classification
- Each line corresponds to a detected metabolite and each column to a studied animal.
- Grayscale cells indicate the intensity of plasma metabolite concentration relative to the average of all samples.
- the boxed graphs represent the phenolic metabolites of the extract of Vaccinium angustifolium, the concentration of which in the plasma has been significantly increased with the treatment according to the invention. The data is displayed as mean ⁇ SEM. ** P ⁇ 0.01 and p * ⁇ 0.05 vs Vaccinium angustifolium B extract: extract of Vaccinium angustifolium.
- G Vitis vinifera extract
- N Agent according to the invention.
- the purpose of this study is to determine whether polyphenols and their metabolic derivatives are able to access the central nervous system, to know if they have effects in the brain.
- 6 control mice (3 adults and 3 elderly) and 20 supplemented mice (10 adults and 10 elderly) were fed a controlled diet free of polyphenols or with a diet enriched with the agent. according to the invention (example 1) for 6 weeks.
- the dose of the agent according to the invention was 500 mg / kg of body weight / day.
- Mice Brains were recovered at the end of the experiment, dissected and stored at -80 ° C.
- the specific polyphenols and connectivitybolHes were measured by high-speed liquid chromatographle UPLC-MS / MS.
- SK-N-SH cells a human neuroblast cell line
- Cells were grown to 80% confluency and then seeded in multi-well cell culture plates to perform different experimental designs.
- the neuroprotective effect of different compounds was analyzed by two different and complementary tests: the cell death quantification test and the cell survival test.
- the cell death test is a colorimetric test based on the measurement of lactate dehydrogenase (LDH) activity released by the cytosol of cells damaged in the supernatant.
- LDH lactate dehydrogenase
- the cell survival test was performed by a Resazurin test.
- Resazurin is an oxidation-reduction indicator of the permeable cell that can be used to monitor the number of viable cells using the tetrazolium compounds. Viable cells with active metabolism can reduce resazurin to resorufin product that is pink and fluorescent.
- the neuronal SK-N-SH cells were subjected to a toxic concentration of hydrogen peroxide (250 ⁇ ) and co-treated with epicatechin, catechin or ferulic acid at 1 ⁇ , lnM and lpM for 24 hours. At the end of the treatment, the cells were washed twice and cell death (LDH release) and survival (Resazurin test) were analyzed. The results showing the effects of the three poh / phenols taken individually after this acute treatment are shown in Figure SA. It is found that the polyphenols taken individually do not protect the cells against hydrogen peroxide.
- neuronal SK-N-SH cells were subjected for 24 hours to a toxic concentration of hydrogen peroxide and co-treated with a mixture (Mix) comprising both epicatechin, catechin and ferulic acid, said mixture being tested at the different concentrations of ⁇ , ln M or lpM.
- a mixture comprising both epicatechin, catechin and ferulic acid, said mixture being tested at the different concentrations of ⁇ , ln M or lpM.
- LDH release cell death
- Resazurin test survival
- the neuroprotective effects of the three polyphenols i.e. epicatechin, catechin and ferulic acid, with cumulative treatment were then studied.
- the SK-N-SH cells were cultured to 80% confluency and then seeded in multi-well cell culture plates. The next day, each of the three polyphenols separately was added to the medium at ⁇ , ln M and lpM for 3 consecutive days. On the third day, the cells were subjected to a toxic concentration of hydrogen peroxide (250 ⁇ ) and the protection was analyzed 24 hours later. At the end of the treatment, the cells were washed twice and cell survival (Resazurin test) was analyzed. Results showing the effects of the three individual polyphenols (Mix) after this cumulative treatment are shown in Figure 5C. It is found that the polyphenols taken individually do not protect the cells against hydrogen peroxide after 3 days of consecutive treatment.
- the purpose of this test is to verify the effectiveness of an agent according to the invention (mixture of Example 2) on the antioxidant status of adult dogs by comparing this efficacy with that of an extract of Vitis vinifera, d an extract of Vaccinium ongustifollum and a control.
- Example 2 the mixture of Example 2 (4 mg / kg of body weight / day).
- the experiment was designed according to a cross test where the dogs were fed experimental rations with the supplementation capsule for 28 days with a break week between each supplementation period. Each dog has received each of four more.
- Plasma samples were taken from the jugular vein before and after each supplementation and held in ice. Plasma was recovered by centrifugation at 2124g whole blood for 10 min at 4 ° C. Plasma aliquots were incubated at 80 ° C.
- Oxidative status was assessed by measuring total antioxidant status (TAS).
- TAS total antioxidant status
- a colorimetric test of the RANDOX laboratories Ref: NX2332, Crumlin, County Antrim, UK
- ABTS 2,2'-azino-di-[3-ethylbenzthiazolone sulphonate]
- metalmyoglobin peroxidase
- hydrogen peroxide to produce the radical cation ABTS *. It has a relatively stable blue-green color, measured at 600 nm.
- the presence of antioxidants in the samples leads to the suppression of the production of this color to a degree proportional to their concentration.
- the SAR is expressed in mmol / L
- ATAS was analyzed using a mixed model.
- the Wilcoxon test was used to compare changes in TAS value before and after supplementation.
- Table 4 The results obtained are presented in Table 4 (mean, standard error and Wilcoxon test) and in Figure 6.
- Table 4 TAS (mmoVL) (mean ⁇ SE ⁇ UD for groups of adult dogs (No. 9) fed with different dietary regimens: agent according to the invention (Invention), extract of Vitis vinlfera fVv). extract of Vacclnlum anaustofotlum (Val or maltodextrin (Control) during 28
- the mixture according to the invention significantly increases the TAS concentration synergistically compared to Vitls vlnifero extract or Vaccinium ongustofolium extract alone.
- the supplementation with a mixture of molecules from Vitis vinifero and Voccinium ongustofolium has a synergistic effect on the total antioxidant status of the animals in comparison with the supplements with an extract of Vitis vinifero and an extract of Voccinium ongustofolium alone .
- the objective of this study is to verify the effect of a mixture according to the invention (example 2) at two doses on the memory levels in dogs.
- the three groups of dogs were then respectively fed with croquettes Inclusion containing either 0 ppm (placebo) or 240 ppm of the mixture of Example 2, 480 ppm of the mixture of Example 2 (ppm relative to the weight of kibble).
- the DNMP test was performed on days - 27 to -16, and the analysis was performed on days 58 to 63.
- the DNMP test test consisted of two phases:
- Phase 1 the dog must move an object placed on one of three possible positions on a food well.
- the block to move covers a reward.
- Urine and blood samples were collected at the beginning of the trial (week 0), after 12 weeks and after 24 weeks.
- the biomarkers were found in amounts below the upper limit obtained with control and experimental treatments at week 0 (CysC plasma, urinary CysC / Crea ratio, urinary cluster / Creat ratio, NGAL plasma, NGAL urinary / creat respectively of 2.23 ⁇ g / mL, 156 ng / g, 443 ng / g, 47 ng / mL, 28.5 ng / g).
- This assay was performed on a 3xTg-AD heterozygous mouse model as described for example in Arsenault D, Dal-Pan A, Tremblay C, Benett DA, Guitton MJ, et al. (2013) PAK Inactivatlon Social Weakness Recognition in 3xTg-AD Mice Barin Deposition of Tau andA ⁇ . The Journal of Neuroscience 33: 10729-10740.
- nontransgenic mice 120 nontransgenic (non-Tg) and triple transgenic (3xTg-AD) mice aged 12 months were used for this assay. Seven mice died before the trial and were excluded. In addition, an additional group of 4-month-old C57BL / 6 mice was used as a control flask.
- Example 1 The agent according to the invention of Example 1 was introduced into mouse pellets.
- the mice were fed for 4 months with a control diet or with 500 mg of extract / kg of body weight / day (reference "Polyphl”) or 2500 mg of extracts / kg of body weight / day (reference "Polyph2" ).
- mice Three months after the start of the trial, behavioral analyzes were performed. After an additional month, the mice are placed under deep anesthesia and intracardiac blood extracts are taken. They are then perfused with intracardiac infusion with phosphate buffered saline containing protease inhibitors and phosphatase inhibitors. Parieto-temporal cortex extracts were then dissected, frozen and kept at -80 ° C. They are then processed for analysis by Elisa, Western blotting and immunofluorescence to measure the following markers: beta-amyloid ( ⁇ , and Tau Neutrophic factor derived from the brain BDNF (Barin derived neurotrophic factor).
- beta-amyloid ⁇
- Tau Neutrophic factor derived from the brain BDNF Barin derived neurotrophic factor
- the administration of the agent according to the invention at doses of 500 or 2500 mg / kg / day prevents deterioration of the memory in 3xTg-AD mice.
- the agent according to the invention makes it possible to prevent the decrease of BDNF (brain-derived neurotrophic factor) in the 16-month-old 3xTg-AD mice.
- BDNF brain-derived neurotrophic factor
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Abstract
Description
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US15/771,328 US11266705B2 (en) | 2015-10-27 | 2016-10-27 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
MYPI2018701631A MY197824A (en) | 2015-10-27 | 2016-10-27 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
SG11201803492TA SG11201803492TA (en) | 2015-10-27 | 2016-10-27 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
CA3002753A CA3002753A1 (fr) | 2015-10-27 | 2016-10-27 | Agent nutritionnel ou therapeutique particulier comprenant un melange de raisin et de bleuet |
EP16794958.5A EP3368055A1 (fr) | 2015-10-27 | 2016-10-27 | Agent nutritionnel ou therapeutique particulier comprenant un melange de raisin et de bleuet |
JP2017515987A JP7084139B2 (ja) | 2015-10-27 | 2016-10-27 | ブドウとブルーベリーの混合体を包含する特定の栄養組成物又は治療組成物 |
AU2016344713A AU2016344713B2 (en) | 2015-10-27 | 2016-10-27 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
KR1020187014968A KR20180103836A (ko) | 2015-10-27 | 2016-10-27 | 포도 및 블루베리 혼합물을 포함하는 특수한 영양용 또는 치료용 제제 |
US17/591,838 US20230024908A1 (en) | 2015-10-27 | 2022-02-03 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
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FR1560263A FR3042712B1 (fr) | 2015-10-27 | 2015-10-27 | Agent nutritionnel ou therapeutique particulier comprenant un melange de raisin et de bleuet |
FR1560263 | 2015-10-27 |
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US15/771,328 A-371-Of-International US11266705B2 (en) | 2015-10-27 | 2016-10-27 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
US17/591,838 Continuation US20230024908A1 (en) | 2015-10-27 | 2022-02-03 | Specific nutritional or therapeutic agent including a mixture of grape and blueberry |
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US (2) | US11266705B2 (fr) |
EP (1) | EP3368055A1 (fr) |
JP (1) | JP7084139B2 (fr) |
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AU (1) | AU2016344713B2 (fr) |
CA (1) | CA3002753A1 (fr) |
FR (1) | FR3042712B1 (fr) |
MY (1) | MY197824A (fr) |
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Cited By (2)
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CN107674451A (zh) * | 2017-09-29 | 2018-02-09 | 安徽中烟工业有限责任公司 | 一种蓝莓色素微胶囊及其制备方法 |
FR3088540A1 (fr) * | 2018-11-21 | 2020-05-22 | Activ'inside | UTILISATION EN PRISE UNIQUE D’UNE COMPOSITION comprenant un melange PARTICULIER D’EXTRAIT DE RAISINS ET D’EXTRAIT DE BLEUETS |
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WO2021072311A1 (fr) | 2019-10-09 | 2021-04-15 | Braini Llc | Compositions comprenant une fibre de peptide de soie de bombyx mori purifié et une huile de graines de buglossoides arvensis raffinée, et procédés associés |
US11707497B2 (en) | 2019-10-09 | 2023-07-25 | Brain Health Holding Llc | Methods and compositions with purified Bombyx mori cocoon silk peptide fiber and refined Buglossoides arvensis seed oil providing anti-inflammatory effects and neuroprotection for disease states |
CN110959735A (zh) * | 2019-12-17 | 2020-04-07 | 天津市尖峰天然产物研究开发有限公司 | 一种添加欧洲越橘提取物的糖果及其制备方法 |
US20230293482A1 (en) * | 2020-03-24 | 2023-09-21 | Shibaura Institute Of Technology | Central nervous system potentiating composition |
FR3109298A1 (fr) * | 2020-04-15 | 2021-10-22 | Activ'inside | Composition pour améliorer les fonctions cognitives |
FR3112686B3 (fr) | 2020-07-24 | 2022-07-29 | Activinside | Composition comprenant un mélange d’extraits de Vitis vinifera et de Vaccinium angustifolium et des probiotiques pour améliorer les fonctions cognitives |
FR3114497B1 (fr) * | 2020-09-29 | 2023-06-02 | Activinside | Composition comprenant des monomères de flavanol et de l’ε-viniférine |
DE202021103977U1 (de) | 2021-07-26 | 2021-08-31 | Activ'inside | Zusammensetzung, die eine Mischung aus Extrakten von Vitis vinifera und Vaccinium angustifolium und Probiotika zur Verbesserung der kognitiven Funktionen enthält |
CN115590874A (zh) * | 2022-12-12 | 2023-01-13 | 汤臣倍健股份有限公司(Cn) | 锦葵素-3-o-葡萄糖苷在制备药物或保健食品的应用 |
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- 2016-10-27 CA CA3002753A patent/CA3002753A1/fr active Pending
- 2016-10-27 WO PCT/EP2016/075905 patent/WO2017072219A1/fr active Application Filing
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- 2016-10-27 KR KR1020187014968A patent/KR20180103836A/ko not_active Application Discontinuation
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FR3088540A1 (fr) * | 2018-11-21 | 2020-05-22 | Activ'inside | UTILISATION EN PRISE UNIQUE D’UNE COMPOSITION comprenant un melange PARTICULIER D’EXTRAIT DE RAISINS ET D’EXTRAIT DE BLEUETS |
WO2020104533A1 (fr) * | 2018-11-21 | 2020-05-28 | Activ'inside | Utilisation en prise unique d'une composition comprenant un melange particulier d'extrait de raisins et d'extrait de bleuets |
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FR3042712B1 (fr) | 2019-05-03 |
AU2016344713A2 (en) | 2018-05-10 |
US11266705B2 (en) | 2022-03-08 |
CA3002753A1 (fr) | 2017-05-04 |
AU2016344713B2 (en) | 2022-03-03 |
EP3368055A1 (fr) | 2018-09-05 |
AU2016344713A1 (en) | 2017-05-04 |
MY197824A (en) | 2023-07-19 |
FR3042712A1 (fr) | 2017-04-28 |
KR20180103836A (ko) | 2018-09-19 |
JP2019500001A (ja) | 2019-01-10 |
JP7084139B2 (ja) | 2022-06-14 |
US20230024908A1 (en) | 2023-01-26 |
US20180303891A1 (en) | 2018-10-25 |
SG11201803492TA (en) | 2018-06-28 |
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