Composition based on extracts of Chrysanthellum americanum and Hibiscus sabdariffa for the prevention and / or treatment of obesity, overweight and / or the yo-yo effect.
A synergistic composition of Chrysanthellum americanum and Hibiscus sabdariffa extracts inhibits adipocyte differentiation and stimulates lipolysis, addressing obesity and yo-yo effect by reducing fat accumulation and improving metabolic health.
Patent Information
- Authority / Receiving Office
- FR · FR
- Patent Type
- Applications
- Current Assignee / Owner
- APOTHEKA ACTIVE INGREDIENTS
- Filing Date
- 2024-11-28
- Publication Date
- 2026-05-29
AI Technical Summary
Existing strategies fail to effectively prevent obesity, overweight, and the yo-yo effect, which are associated with metabolic complications such as type 2 diabetes and cardiovascular disease, and often have adverse side effects.
A composition combining extracts of Chrysanthellum americanum and Hibiscus sabdariffa, which synergistically inhibit adipocyte differentiation, reduce lipid storage, and stimulate lipolysis, thereby regulating lipid metabolism and reducing fat accumulation.
The composition effectively reduces body fat mass, improves lipid metabolism, reduces inflammation, and enhances insulin sensitivity, providing a sustainable solution for obesity and yo-yo effect management with minimal side effects.
Abstract
Description
Title of the invention: Composition based on extracts of Chrysanthellum americanum and Hibiscus sabdariffa for the prevention and / or treatment of obesity, overweight and / or the yo-yo effect.
[0001] The present invention relates to the prevention and / or control of obesity and / or overweight and / or the yo-yo effect in humans or animals.
[0002] Obesity, characterized by an excessive accumulation of body fat, is a major health problem worldwide, contributing to metabolic complications such as type 2 diabetes, cardiovascular disease, and metabolic syndrome. It is therefore crucial to develop strategies to prevent fat accumulation and promote the reduction of adipose tissue.
[0003] The yo-yo effect, also known as weight cycling, weight swings, or weight fluctuation, is characterized by a rapid regain of the weight lost after dieting, often accompanied by a further increase in fat mass. This phenomenon, which results from significant fluctuations in body weight, is a common problem in obesity management and can exacerbate health risks, notably by increasing insulin resistance, exacerbating cardiovascular disease, and disrupting metabolism. It is therefore essential to develop sustainable solutions to prevent the yo-yo effect and promote stable and healthy weight loss.
[0004] To achieve this objective, the invention relates to compositions comprising a mixture consisting of at least one extract of Hibiscus sabdariffa and one extract of Chrysanthellum americanum, and / or a single extract obtained from at least one extract of Hibiscus sabdariffa and Chrysanthellum americanum. These two plant species have already been described and used in nutritional products, but unexpectedly, their combination leads to surprising and synergistic results in the management of body fat, acting on different metabolic mechanisms. These plants act synergistically to target key metabolic pathways involved in the formation and accumulation of lipids, thus contributing to better body weight management.
[0005] Advantageously, the compositions according to the invention act on lipid accumulation in preadipocytes (adipogenesis).
[0006] Lipid accumulation in preadipocytes, also called adipogenesis, is the process by which precursor cells called preadipocytes differentiate into mature adipocytes capable of storing fats in the form of triglycerides. This process is essential in the regulation of adipose tissue mass in the body.
[0007] This mechanism begins with the differentiation of preadipocytes: Under the influence of various hormonal (such as insulin) and nutritional signals, preadipocytes transform into mature adipocytes. This process is activated by key transcription factors such as PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) and C / EBP (CCAAT / enhancer-binding proteins).
[0008] Once differentiated, adipocytes accumulate lipids in the form of triglycerides. This allows these cells to store excess energy in response to a diet rich in fats or sugars.
[0009] The increase in the number and size of adipocytes contributes to the increase in total adipose tissue in the body, which leads to weight gain.
[0010] The compositions described in the invention therefore act by regulating lipid accumulation in preadipocytes, which can be achieved through several mechanisms: - Inhibition of preadipocyte differentiation: By preventing preadipocytes from differentiating into mature adipocytes, the compositions limit the number of cells capable of storing fat. This reduces the body's overall capacity to accumulate fat. - Reduction of lipid storage: By reducing the expression of genes related to lipogenesis (fat synthesis), the compositions decrease the accumulation of triglycerides in adipocytes. The cells therefore store less lipids, which reduces the size of the adipocytes. - Stimulation of lipolysis: Certain molecules present in plant extracts (such as polyphenols or flavonoids) stimulate lipolysis, the process by which triglycerides stored in adipocytes are broken down into free fatty acids and glycerol, which are then used as an energy source. This leads to a reduction in the volume of fat cells.
[0011] The compositions according to the invention therefore have a fat-reducing effect: By decreasing the accumulation of fat in adipocytes and stimulating the breakdown of existing fat, the compositions reduce body fat mass. This has a direct impact on reducing overweight, obesity, and / or the yo-yo effect.
[0012] Furthermore, by limiting excessive fat accumulation, the compositions can improve lipid metabolism, reduce inflammation associated with obesity and / or the yo-yo effect, and improve insulin sensitivity. This can help prevent metabolic complications such as type 2 diabetes or cardiovascular disease.
[0013] Furthermore, they present few or no side effects compared to those observed with existing treatments and those under development. The invention therefore aims at the use of the compositions as food supplements, products nutritional or health products, including medicines, particularly to prevent and / or combat obesity and / or overweight and / or the yo-yo effect in humans or animals, improve lipid metabolism, reduce inflammation associated with obesity, and improve insulin sensitivity.
[0014] As used in the application, the yo-yo effect, also called weight cycling, weight fluctuation, or weight swings, refers to a phenomenon where a person experiences significant and repeated variations in their body weight. After a period of weight loss, often linked to a restrictive diet, the lost weight is quickly regained when the person stops dieting, and it may even be exceeded. This cycle of weight loss and regain can be repeated several times, generating significant fluctuations in body mass.
[0015] In this application, the singular or plural shall be used interchangeably to refer to the compositions according to the invention.
[0016] According to a first embodiment, the composition according to the invention comprises at least one mixture consisting of at least: an extract of Chrysanthellum americanum, and an extract of Hibiscus sabdariffa.
[0017] Chrysanthellum americanum (sometimes also called Chrysanthellum indicum ssp. americanum) is a plant belonging to the Asteraceae family. It is a small perennial herbaceous plant native mainly to Africa and South America, often used for its medicinal properties in herbal medicine.
[0018] The main bioactive components present in Chrysanthellum americanum include: Flavonoids: Chrysanthellin A and B, luteolin, apigenin. Saponins: Contribute to its anti-inflammatory and hepatic effects. Phenolic acids: Caffeic acid, chlorogenic acid.
[0019] Hibiscus sabdariffa, also known as roselle or Guinea sorrel, is an annual herbaceous plant belonging to the Malvaceae family. Native to West Africa, it is now cultivated in many tropical and subtropical regions of the world for its culinary and medicinal properties.
[0020] The main bioactive components present in Hibiscus sabdariffa include: Anthocyanins: Delphinidin-3-sambubioside, cyanidin-3-sambubioside (responsible for the red color of the calyx). Organic acids: Hibisciic acid, malic acid, citric acid, tartaric acid, which contribute to its tangy taste. Flavonoids: Quercetin, gossypetin, myricetin, which have antioxidant and anti-inflammatory properties. Protocatechuic acid: Known for its antioxidant and anti-inflammatory effects.
[0021] Surprisingly, these two extracts act synergistically on lipid metabolism.
[0022] For the purposes of this invention, a plant extract "X" or plant raw material "X" is defined as a set of molecules obtained from plant "X" by any suitable process. Examples include aqueous extracts (obtained using an aqueous solvent), alcoholic extracts (obtained using an alcoholic solvent), extracts using an organic solvent, or extracts using a natural fat or a mixture of natural fats, particularly a vegetable oil or a mixture of vegetable oils. An aqueous solvent is defined as any solvent consisting wholly or partly of water. Examples include 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. Ethanol is a notable example of an alcoholic solvent.
[0023] For the purposes of this invention, plant or plant raw material means the whole plant or part of a plant, including cell cultures, which has not yet undergone any specific treatment and is intended to be used in the manufacture of a plant preparation.
[0024] Plant 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 possibly incorporation of additives homogenization packaging.
[0025] The extract of Chrysanthellum americanum or the single extract is preferably obtained from the whole plant and / or aerial parts of Chrysanthellum americanum, preferably the leaves.
[0026] The aerial parts of a plant include all structures located above the ground, such as stems, leaves, flowers, and fruits.
[0027] The extract may in particular be a hydroalcoholic or aqueous extract or subcritical / supercritical CO2 or subcritical H2O or associated with a heat treatment being carried out by conventional heating or under microwave frequency or under ultrasound.
[0028] The plant / extract ratio is preferably between 1 / 1 and 100 / 1, between 1 / 1 and 75 / 1, between 1 / 1 and 50 / 1, and preferably between 1 / 1 and 25 / 1.
[0029] The composition according to the invention, when intended for human use, preferably comprises an amount of Chrysanthellum americanum extract allowing the administration of an amount between 0.00001g and 0.05g, 0.0001g and 0.05g, 0.001g and 0.05g, 0.01g and 0.05g, 0.025g and 0.05g, 0.04g and 0.05g, preferably between Xg and Xg, of Chrysanthellum americanum extract per kg of body weight of the person to whom the composition is administered and per day.
[0030] Preferably, the extract of Chrysanthellum americanum comprises molecules selected from chrysanthellin A, chrysanthellin B, apigenin, luteolin, eriodictyol, isoschaftoside, and their glycosylated derivatives such as apigenin-7-O-glucoside, luteolin-7-O-glucoside, and eriodictyol-7-O-glucoside, phenolic acids such as caffeic acid and chlorogenic acid, as well as triterpenic saponins, or their analogues.
[0031] For the purposes of this invention, analogues are understood to mean any compound having a chemical structure similar to another compound, but differing from it by a certain component. It may differ by one or more atoms, functional groups, or substructures, which are replaced by other atoms, functional groups, or substructures.
[0032] The extract ^Hibiscus sabdariffa or the single extract is preferably obtained from the whole plant and / or aerial parts ^Hibiscus sabdariffa, preferably the flowers.
[0033] This may in particular be a hydroalcoholic or aqueous extract or subcritical / supercritical CO2 or subcritical H2O or associated with a heat treatment being carried out by conventional heating or under microwave frequency or under ultrasound.
[0034] The plant / extract ratio is preferably between 1 / 1 and 100 / 1, between 1 / 1 and 75 / 1, between 1 / 1 and 50 / 1, and preferably between 1 / 1 and 25 / 1.
[0035] The composition according to the invention, when intended for human use, preferably comprises a quantity of Hibiscus sabdariffa extract allowing the administration of an amount between 0.00001g and 0.05g, 0.0001g and 0.05g, 0.001g and 0.05g, 0.01g and 0.05g, 0.025g and 0.05g, 0.04g and 0.05g, preferably between Xg and Xg, of Hibiscus sabdariffa extract per kg of body weight of the person to whom the composition is administered and per day.
[0036] Preferably, the Hibiscus sabdariffa extract comprises molecules selected from delphinidine-3-sambubioside, cyanidin-3-sambubioside, and their glycosylated derivatives, phenolic acids such as hibiscic acid, chlorogenic acid, protocatechuic acid, and caffeic acid, flavonoids such as quercetin, gossypetin, and myricetin, or their analogues.
[0037] For the purposes of this invention, a mixture is defined as the combination of at least two extracts in solid, liquid, or gaseous form, which may or may not interact chemically. The mixture of extracts according to the invention is obtained by any process known to those skilled in the art. It may be obtained by simply mixing the extracts.
[0038] Preferably, the ratio of Chrysanthellum americanum extract / Hibiscus sabdariffa extract in the mixture is between 0.001 / 0.001 and 10 / 10, 0.01 / 0.01 and 5 / 5, 0.1 / 0.1 and 1 / 1.
[0039] According to one embodiment, in addition to the mixture consisting of several plant extracts or instead of the mixture consisting of several plant extracts, the composition according to the invention may comprise at least one single extract obtained from a mixture of at least two plants or plant raw materials chosen from Chrysanthellum americanum and Hibiscus sabdariffa.
[0040] A single extract obtained from several plants "X" or plant raw materials "X" within the meaning of the invention is understood to be a set of molecules obtained from a mixture of at least two plants "X" by any suitable process, in other words, a "co-extraction". Examples include aqueous extracts (obtained using an aqueous solvent), alcoholic extracts (obtained using an alcoholic solvent), extracts using an organic solvent, or extracts using a natural fat or a mixture of natural fats, in particular a vegetable oil or a mixture of vegetable oils. An aqueous solvent is understood to be any solvent consisting wholly or partly of water. Examples include 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. Ethanol is an example of an alcoholic solvent.For the purposes of this invention, "plant" or "plant raw material" means the whole plant or part of a plant, including cell cultures, that has not yet undergone any specific treatment and is intended for use in the manufacture of a plant preparation. The single extract of a mixture of plants "X" can be obtained by any suitable co-extraction process, for example, by a process comprising the following steps: solid / liquid extraction, separation / pressing, filtration, evaporation-drying, optionally incorporation of additives, homogenization-packaging.
[0041] Surprisingly, the inventors discovered that co-extraction of Chrysanthellum americanum and Hibiscus sabdariffa resulted in higher extraction yields than the theoretical yield. This phenomenon is explained by the synergy between the two plants, which appears to improve the solubility and release of bioactive compounds during the extraction process.
[0042] Advantageously, this increased yield allows for a higher concentration of bioactive molecules, thereby enhancing the effectiveness of the compositions according to the invention. This effectiveness is not only optimized for managing lipid metabolism, but also for the antioxidant, anti-inflammatory, and hepatoprotective properties of the extracts.
[0043] Furthermore, a higher extraction yield contributes to reduced production costs by requiring less raw material to obtain comparable concentrations, while also making the process more environmentally friendly by reducing the amount of solvents needed. Thus, co-extraction offers a significant economic and environmental advantage, while also improving the therapeutic properties of the extracts obtained.
[0044] The whole plant or the aerial parts of Chrysanthellum americanum, preferably the leaves, are preferably used as raw material plant to obtain the unique extract. The unique extract is preferably made from at least 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20%, 30%, 50%, 75%, up to 95% of whole plant or aerial parts of Chrysanthellum americanum by weight relative to the total weight of the mixture of plants used to make the unique extract.
[0045] The whole plant or aerial parts of Hibiscus sabdariffa, preferably the flowers, are preferably used as the plant raw material for obtaining the single extract. The single extract is preferably made from at least 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20%, 30%, 50%, 75%, up to 95% of the whole plant or aerial parts of Hibiscus sabdariffa by weight relative to the total weight of the plant mixture used to make the single extract.Preferably, the single extract comprises: molecules from Chrysanthellum americanum selected from chrysanthellin A, chrysanthellin B, apigenin, luteolin, eriodictyol, isoschaftoside, and their glycosylated derivatives such as apigenin-7-O-glucoside, luteolin-7-O-glucoside, and eriodictyol-7-O-glucoside; phenolic acids such as caffeic acid and chlorogenic acid, as well as triterpenic saponins or their analogues; molecules from Hibiscus sabdariffa selected from delphinidin-3-sambubioside, cyanidin-3-sambubioside, and their glycosylated derivatives; phenolic acids such as hibiscic acid, chlorogenic acid, protocatechuic acid, and caffeic acid; and flavonoids such as Quercetin, gossypetin, and myricetin, or their analogues.
[0046] The composition according to the invention comprising a single extract, when intended for human use, preferably comprises an amount of single extract corresponding to an administration of an amount between 0.00001g and 0.05g, 0.0001g and 0.05g, 0.001g and 0.05g, 0.01g and 0.05g, 0.025g and 0.05g, 0.04g and 0.05g, preferably between Xg and Xg of single extract per kg of body weight of the person to whom the composition is administered and per day.
[0047] Preferably, the Chrysanthellum americanum / Hibiscus sabdariffa ratio used in the co-extraction is between 0.001 / 0.001 and 10 / 10, 0.01 / 0.01 and 5 / 5, 0.1 / 0.1 and 1 / 1.
[0048] According to one embodiment, the single extract is obtained from: - between 0.1% and 95%, 0.5% and 75%, 1% and 50%, 2% and 40%, 5% and 30%, 10% and 20%, preferably between 40% and 60%, more preferably between 45% and 55% of Hibiscus sabdariffa by weight relative to the total weight of the plant mixture used to make the single extract; and - between 0.1% and 95%, 0.5% and 75%, 1% and 50%, 2% and 40%, 5% and 30%, 10% and 20%, preferably between 40% and 60%, more preferably between 45% and 55% of Chrysanthellum americanum by weight relative to the total weight of the plant mixture used to make the unique extract.
[0049] The compositions according to the invention, in their various versions, may consist exclusively of the elements described (plant extracts and / or single extract(s)), or may also include at least one additional element (products, molecules, extracts, active ingredients, excipients, etc.) added in addition to the plant extracts and / or the single extract(s), said additional element preferably being chosen from: - the following vitamins: B1, B2, B3, B5, B6, B8, B9, B12, C, A, D, E, K1 and K2; - the following compounds: amino acids, antioxidants, obeticholic acid, corosolic acid, polyunsaturated fatty acids of the omega 6 and / or omega 3 family, orotic acid, pangamic acid, para-aminobenzoic acid, amygdalin, beta-glucans, camitin, dimethylglycine, imeglimin, isoflavones, L-arginine, oxytocin, pectin, pyridoxamine, resveratrol, viniferine, L-citrulline; - the following trace elements and minerals: arsenic, boron, calcium, copper, iron, fluorine, iodine, lithium, manganese, magnesium, molybdenum, nickel, phosphorus, selenium, vanadium, zinc; - the following non-essential microconstituents: conjugated linolenic acid, lipoic acid, carotenoids, camitin, choline, coenzyme Q10, phytosterols, polyphenols of the tannin and lignan family, taurine; - fructo-oligosaccharides, galacto-oligosaccharides; - lactic acid bacteria; - yeasts, for example red yeast rice (Monascus purpureus); - mushrooms, for example maitake; - insect-derived products compatible with the food and pharmaceutical sectors; - marijuana and hashish; - coating agents: for example hypromellose, microcrystalline cellulose, stearic acid, talc, sugar, shellac, povidone, beeswax; - flavourings: for example natural blueberry flavouring or natural strawberry flavouring; - acidifiers such as malic acid; - anti-caking agents: for example silicon dioxide or magnesium stearate; - thickeners such as xanthan gum, colloidal silica, mono and diglycerides of fatty acids; - stabilizers such as calcium phosphate; - emulsifiers such as soy lecithin; - bulking agents such as corn starch; - excipients: for example microcrystalline cellulose, magnesium stearate or dicalcium phosphate.
[0050] The compositions according to the invention, in their various variants, may also include at least one additional element for the treatment of diabetes (products, molecules, extracts, active ingredients, excipients, etc.) added in addition to the plant extracts and / or the single extract(s), said additional element being preferentially chosen from: metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, insulin, sulfonylureas, glinides, thiazolidinediones, acarbose, soluble fibers, ginseng, turmeric, berberine, cinnamon, chromium, magnesium, quercetin, as well as various stabilizing excipients, prolonged-release agents, and molecules facilitating the absorption of the active ingredients.
[0051] The compositions according to the invention can be in any form, including capsules, tablets, softgels, powder, gel, emulsion, liquid form, sticks, sachets, ampoules, dropper or injectable form.
[0052] The compositions according to the invention can be used as nutraceutical compositions, nutrition products or health products, in particular as medicines.
[0053] A nutraceutical composition is defined as a formulation containing natural substances or plant extracts that provide nutritional and physiological benefits, often intended to improve health, prevent disease, or support specific bodily functions. The term "nutraceutical" is a combination of the words "nutrition" and "pharmaceutical," and refers to products that lie at the intersection of food and medicine.
[0054] Nutritional product means all products having a nutritional and / or physiological effect, including in particular food supplements, foods, dietetic products, etc. These products are in particular administrable by oral, gastric or intravenous route.
[0055] The term "health product" refers to all products having a beneficial effect on health, whether for prevention or treatment, and whether this effect is physiological or pharmacological, including medicines and pharmaceutical products. These products are particularly administrable by oral, gastric, intravenous, or cutaneous routes.
[0056] The compositions according to the invention can be used in the regulation of lipid metabolism, preferably to reduce the accumulation of fat in human adipose tissue.
[0057] The compositions according to the invention can be used to prevent and / or combat obesity and / or overweight and / or the yo-yo effect, preferably by reducing lipid accumulation in preadipocytes (adipogenesis). This also allows for improved lipid metabolism, reduced inflammation associated with obesity and / or the yo-yo effect, and improved insulin sensitivity.
[0058] According to another aspect of the invention, the invention relates to a method for preparing a plant extract comprising a co-extraction of Hibiscus sabdariffa and Chrysanthellum americanum, characterized in that the extraction is carried out simultaneously from selected parts of the plants, preferably the aerial parts of Hibiscus sabdariffa, more preferably the flowers of Hibiscus sabdariffa and preferably the aerial parts of Chrysanthellum americanum, more preferably the leaves of Chrysanthellum americanum.
[0059] According to one embodiment, the extraction is carried out using an aqueous or hydroalcoholic solvent, preferably a solvent containing between 20% and 80% ethanol.
[0060] According to another aspect of the invention, the invention relates to a method for treating human adipose tissue and / or for treating and / or preventing obesity and / or overweight and / or the yo-yo effect, comprising administering a therapeutically effective amount of the composition according to the invention to a subject in need of regulation of body fat accumulation.
[0061] By "therapeutically effective quantity" is meant a quantity of the pharmaceutical composition administered to a subject that is sufficient to produce the desired therapeutic effect, without causing significant undesirable side effects.
[0062] As used herein, the term "subject" refers to an animal, preferably a mammal, in particular a human, pig, chimpanzee, dog, cat, cow, mouse, rabbit, or rat. Even more preferably, the subject is a human being, including an adult, a child, and a human being in the prenatal stage.
[0063] As used herein, the term "treatment" refers to any act intended to improve the health status of patients, such as therapy, prevention, prophylaxis, and disease delay. In some embodiments, this term refers to the improvement or eradication of a disease or symptoms associated with a disease. In other embodiments, this term refers to the minimization of the spread or worsening of the disease resulting from the administration of one or more therapeutic agents to a subject suffering from such a disease.
[0064] In a medical setting, this composition can be formulated in various dosage forms, such as tablets, capsules, injectable solutions, or oral suspensions.
[0065] The formulation of a suitable composition can be achieved using standard pharmaceutical chemicals and formulation methodologies, all of which are readily available to those skilled in the art. For example, the composition according to the invention can be combined with one or more pharmaceutically acceptable excipients or vehicles.
[0066] Auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, reducing agents, and the like, may be present in the excipient or vehicle. Suitable reducing agents include cysteine, thioglycerol, thioreducin, glutathione, and the like. Excipients, vehicles, and auxiliary substances are generally pharmaceutical agents that do not induce an immune response in the individual receiving the composition and that can be administered without excessive toxicity.
[0067] Pharmaceutically acceptable excipients include, but are not limited to, liquids such as water, saline solution, polyethylene glycol, hyaluronic acid, glycerol, thioglycerol, and ethanol. Pharmaceutically acceptable salts may also be included, for example, salts of mineral acids such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and salts of organic acids such as acetates, propionates, malonates, benzoates, and the like.
[0068] Such compositions may be prepared, packaged, or sold in a form suitable for bolus or continuous administration. Injectable compositions may be prepared, packaged, or sold in unit-dose form, for example, in ampoules or in preservative-containing multidose containers. Compositions include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and extended-release or biodegradable implantable formulations.
[0069] Such compositions may further include one or more additional ingredients including, but not limited to, suspending, stabilizing or dispersing agents. DESCRIPTION OF THE FIGURES
[0070] [Fig.1]: Evaluation of the lipid index by labeling lipid droplets with Bodipy at the end of the culture: the results are expressed as % of the respective controls. - As a percentage of differentiated cells for the undifferentiated condition - As a percentage of DMSO for the GW9662 conditions (antagonist of PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) receptors), which play a role crucial in the regulation of lipid and carbohydrate metabolism, as well as in inflammation and adipose cell differentiation) and the active ingredients. Comparison of A (Co-extract 1 / 110 pg / ml) versus B (Chrysanthellum 5 pg / ml) and C (Hibiscus 5 pg / ml). A greater reduction is observed in A compared to B and C at the same concentrations.
[0071] [Fig.2]: Evaluation of the lipid index by labeling lipid droplets at the end of the culture, comparison of conditions A, B and C. Condition A was set at 100%, B and C were expressed as a % of A.
[0072] EXAMPLES
[0073] Example 1 - Adipogenesis on 3 human preadipocyte donors
[0074] The co-extract of Hibiscus sabdariffa and Chrysanthellum americanum (Product A), the extract of Chrysanthellum americanum (Product B) and the extract of Hibiscus sabdariffa (Product C) were tested at a concentration of 10 pg / ml for A and 5 pg / ml for B and C.
[0075] In parallel, the effect of the equivalent DMSO solvent at these doses was also evaluated. A stock solution was prepared directly in DMSO and diluted 1 / 1000 in the culture medium. Thus, for the study of adipogenesis, the results can be compared to those of DMSO diluted 1 / 1000.
[0076] [Tables 1] Product Code Solvent Tested Concentration (pg / m³) Co-extract of Chibiscus sabdariffa and Chrysanthellum americanum A DMSO 10 Extract of Chrysanthellum americanum B DMSO 5 Extract of Chibiscus sabdariffa C DMSO 5
[0077] Adipogenesis induction was performed on 3 donors: Donor 1: Woman, 34 years old, abdominal area, BMI: 30 kg / m2 Donor 2: Woman, 34 years old, abdominal area, BMI: 23.4 kg / m2 Donor 3: Woman, 28 years old, abdominal area, BMI: 21 kg / m2
[0078] According to the following protocol: Digestion of subcutaneous adipose tissue taken from donors, isolation of preadipocytes, differentiation of cells jointly with treatment with actives A, B, C or control for 12 / 13 days, fluorescent labeling and automatic quantification of lipid droplets and nuclei (in final time, J12 / J13).
[0079] Statistical analyses:
[0080] All statistical analyses were performed using the means obtained for each of the three donors. Two statistical tests were used to evaluate the significant differences between the different conditions, considering non-parametric and unpaired data. - To compare two conditions: unpaired t-test - To evaluate the effect of an active ingredient (at 3 doses) in comparison with the solvent DMSO, a one-way ANOVA test with multiple comparisons by Dunnett was carried out.
[0081] Significant differences were noted according to the following logic: *p-value<0.05 / **p-value<0.01 / ***p-value<0.001 / ****p-value <0.0001
[0082] See [Fig. 1] for the evaluation of the lipid index by labeling lipid droplets with Bodipy at the end of the culture: the results are expressed as % of the respective controls. - As a percentage of differentiated cells for the undifferentiated condition - As a percentage of DMSO for conditions GW9662 and assets
[0083] A greater reduction of A is observed versus B and C at the same concentrations.
[0084] Statistics were carried out in order to compare condition A with conditions B and C. See [Fig.2]: Condition A was set at 100%, B and C were expressed as a % of A.
[0085] The p-values obtained from the comparisons are presented below.
[0086] [Tables2] Lipid index (p-values) A vs B 0.0226 t-test AvsC 0.0496 t-test A vs B and CB: 0.0281 / C: 0.1119 ANOVA
[0087] Statistical analysis: unpaired t-test and one-way Dunnett's ANOVA with multiple comparisons
[0088] In conclusion, we surprisingly observe a synergistic effect of a co-extract of Chrysanthellum americanum and A Hibiscus sabdariffa since at identical concentrations A / B / C ([A] corresponding to [B]+[C]) the lipid index obtained with product A is significantly lower than the isolated extracts at the same concentration, suggesting an effect on lipid accumulation and an effect on weight management, in particular to prevent the yo-yo effect.
[0089] Example 2 - _ Extraction yields
[0090] Three plant extracts named MP 1 (Chrysanthellum americanum leaves), MP 2 (Hibiscus sabdariffa flowers) and MP 3 (Hibiscus flower mixture) sabdariffa and Chrysanthellum americanum leaves) were treated under the following conditions:
[0091] First, 450 milliliters of plant material was measured before being placed in a 3-liter flask containing 1.95 liters of ethanol at 30 degrees. The mixture was then homogenized by mechanical stirring at 300 to 350 revolutions per minute. The dispersion was then heated at 50 degrees Celsius for 13 hours and 15 minutes. Next, the mixture was filtered through a 100-micrometer cutoff under slight overpressure (0.5–1 bar relative). The filtrate was concentrated approximately 3 times at 50–55 degrees Celsius under a partial vacuum of 90 millibars absolute for approximately 11 hours. The pre-concentrated filtrate was then heat-treated at 100 degrees Celsius for 45 minutes. Then, the medium was concentrated again under the same conditions for about 6 hours before being placed in a vacuum oven at 55 degrees Celsius between 60 and 150 millibars absolute.Following the overflow of the MP 1 extract, the vacuum was limited to 150 millibars absolute. After 16 hours of drying under these conditions, the product was placed in a ventilated oven at 55 degrees Celsius for at least 3 days, until its mass stabilized for at least 48 hours. At the end of the drying process, the product had to be crumbled and then ground in a mortar to obtain a powder. Here again, the previously mentioned technologies would allow for a more easily handleable product.
[0092] The mass obtained at the end of the extraction was measured and compared to the mass of material used for each extract in order to determine a yield for each extraction:
[0093] [Tables3] Chrysanthellum Hibiscus Co-extraction Yield (%) 20% 47% 37% Theoretical co-extraction yield (m / m) 33.5%
[0094] Surprisingly, the mass obtained at the end of extraction corresponds to 37% of the mass of MP 3 used, which is a mixture of MP 1 and MP 2. This yield is higher than the expected theoretical yield of 33.5%.
[0095] This unexpected effect demonstrates a synergy between the components of MP 1 and MP 2 during the extraction process, resulting in a more efficient release of the active compounds. This increased yield is not only advantageous in terms of industrial productivity, but it also improves the concentration of bioactive molecules in the final composition.
Claims
Demands
1. Composition comprising at least: - a mixture consisting of at least one extract of Hibiscus sabdariffa and one extract of Chrysanthellum americanum, and / or - a single extract obtained from at least Hibiscus sabdariffa and Chrysanthellum americanum.
2. Composition according to claim 1, characterized in that the extract of Chrysanthellum americanum or the single extract is obtained from whole plant and / or aerial parts of Chrysanthellum americanum, preferably the leaves.
3. Composition according to any one of claims 1 to 2, characterized in that the Hibiscus sabdariffa extract or single extract is obtained from whole plant and / or aerial parts of Hibiscus sabdariffa, preferably the flowers.
4. Composition according to any one of claims 1 to 3, characterized in that the ratio of Chrysanthellum americanum extract / Hibiscus sabdariffa extract in the mixture is between 0.001 / 0.001 and 10 / 10, 0.01 / 0.01 and 5 / 5, 0.1 / 0.1 and 1 / 1.
5. Composition according to any one of claims 1 to 4, characterized in that it is formulated in the form of capsules, tablets, softgels, powder, gel, emulsion, liquid form, sticks, sachets, ampoules, dropper or injectable form.
6. Composition according to any one of claims 1 to 5, characterized in that it also comprises at least one additional element added in addition to the plant extracts or the single extract, said additional element being selected from: - the following vitamins: B1, B2, B3, B5, B6, B8, B9, B12, C, A, D, E, K1 and K2; - the following compounds: amino acids, antioxidants, obeticholic acid, corosolic acid, polyunsaturated fatty acids of the omega 6 and / or omega 3 family, orotic acid, pangamic acid, para-aminobenzoic acid, amygdalin, beta-glucans, camitin, dimethylglycine, imeglimin, isoflavones, L-arginine, oxytocin, pectin, pyridoxamine, resveratrol, viniferine, L-citrulline; - the following trace elements and minerals: arsenic, boron, calcium, copper, iron, fluorine, iodine, lithium, manganese, magnesium, molybdenum, nickel, phosphorus, selenium, vanadium, zinc; - the following non-essential microconstituents: conjugated linolenic acid, lipoic acid, carotenoids, carnitine, choline, coenzyme Q10, phytosterols, polyphenols of the tannin and lignan families, taurine; - fructo-oligosaccharides, galacto-oligosaccharides; - lactic acid bacteria; - yeasts, for example red yeast rice (Monascus purpureus); - mushrooms, for example maitake; - insect-derived products compatible with the food and pharmaceutical sectors; - marijuana and hashish; - coating agents: for example hypromellose, microcrystalline cellulose, stearic acid, talc, sugar, shellac, povidone, beeswax;- Flavorings: for example, natural blueberry flavoring or natural strawberry flavoring; - Acidifiers such as malic acid; - Anti-caking agents: for example, silicon dioxide or magnesium stearate; - Thickeners such as xanthan gum, colloidal silica, mono- and diglycerides of fatty acids; - Stabilizers such as calcium phosphate; - Emulsifiers such as soy lecithin; - Bulking agents such as corn starch; - Excipients: for example, microcrystalline cellulose, magnesium stearate, or dicalcium phosphate.
7. A process for preparing a plant extract comprising a co-extraction of Hibiscus sabdariffa and Chrysanthellum americanum, characterized in that the extraction is carried out simultaneously from selected parts of the plants, preferably the aerial parts of Hibiscus sabdariffa, more preferably the flowers of Hibiscus sabdariffa and preferably the aerial parts of Chrysanthellum americanum, more preferably the leaves of Chrysanthellum americanum.
8. A preparation method according to claim 7, characterized in that the extraction is carried out using an aqueous or hydroalcoholic solvent, preferably a solvent containing between 20% and 80% ethanol.
9. Composition according to any one of claims 1 to 6, for its use in the regulation of lipid metabolism, preferably to reduce the accumulation of fat in human adipose tissue.
10. Composition according to any one of claims 1 to 6, for its use in the prevention and / or control of obesity and / or overweight and / or the yo-yo effect, preferably by reducing lipid accumulation in preadipocytes (adipogenesis).