US20100028464A1 - Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a sateity agent for treatment of obesity - Google Patents

Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a sateity agent for treatment of obesity Download PDF

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US20100028464A1
US20100028464A1 US12/298,242 US29824207A US2010028464A1 US 20100028464 A1 US20100028464 A1 US 20100028464A1 US 29824207 A US29824207 A US 29824207A US 2010028464 A1 US2010028464 A1 US 2010028464A1
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satiation
satiation agent
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Cedric Bourges
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/10—Natural spices, flavouring agents or condiments; Extracts thereof
    • A23L27/11—Natural spices, flavouring agents or condiments; Extracts thereof obtained by solvent extraction
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/10—Natural spices, flavouring agents or condiments; Extracts thereof
    • A23L27/115—Natural spices, flavouring agents or condiments; Extracts thereof obtained by distilling, stripping, or recovering of volatiles
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/11—Aldehydes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • This invention relates to the use of the active ingredients of saffron, in particular safranal, crocin, picrocrocin and derivatives thereof, for an application as a satiation agent.
  • a satiation agent is useful in particular for the treatment of obesity, for reducing or at least controlling the intake of calories consumed daily so as to regulate body weight.
  • a satiation agent will allow the consumer, based on the alteration of the sensation of fullness, to control his physical appearance and/or to treat his health problems linked to overweight.
  • the current diet is low in fruits and vegetables but in contrast very high in fat and heavy on sugar, meat and alcohol.
  • water consumption is gradually being replaced by the consumption of sugary carbonated beverages.
  • This dietary malnutrition brings about an increase in the number of calories consumed daily and thus a possible weight gain.
  • An invasive solution consists in the installation of a gastric ring so as to separate the stomach into two parts. Although this solution causes the sensation of hunger to disappear upon the ingestion of the first mouthfuls of a meal, the fact remains that this solution is used only in cases of extreme overweight. In addition, the risk of this surgical operation is significant.
  • Another approach in the treatment of overweight is the use of satiation agents so as to reduce the intake of energy, and therefore the weight.
  • the latter are most often contained in the food product that is to be consumed.
  • satiation agents are released directly into the stomach (WO 02/00042), and others act in different parts of the intestine so as to modify the response of the ileal brake (U.S. Pat. No. 6,267,988, U.S. Pat. No. 5,753,253, DE 2701361) or else some increase secretion of ⁇ -MSH by inhibiting the reuptake of dopamine or serotonin.
  • the document WO 01/17541 discloses a composition that comprises proteins, a high level of calcium, long-chain fatty acids, and an inhibitor source of the protease that is extracted from the potato so as to induce satiation.
  • the document WO 01/17377 discloses polysaccharides that contain uronic acid and that are cross-linked to one another so as to form a sponge-type structure that dissolves poorly in water, in stomach fluids and in the intestine or can be poorly resorbed. This composition has the purpose of providing a satiation effect.
  • US 2006/0040003 describes a composition for improving the satiation before and after the meal by raising the level of serotonin.
  • This composition comprises natural substances such as, i.a., niacin, vitamin B6, calcium, phosphorus, magnesium, chitosan, and ginseng.
  • compositions as described in the prior art have various drawbacks: the sensation of fullness does not always last very long.
  • the food preparations (soups, bars) that contain the products are generally not very appetizing for the consumer.
  • these compositions are not always easy to produce; some actually are not stable during the production process and/or storage, altering the taste, the odor and the texture of the final product.
  • they optionally can have detrimental interactions with other active substances such as vitamins or minerals.
  • products that contain synthetic chemical compounds, such as polymers tend to discourage the consumer from purchasing them. This is why natural compounds are preferred.
  • Saffron is known in the prior art only as a stimulator of the gastric function, bitterness regulator, in particular after the intake of peppers (JP 2005 143308), or else it is used so as to improve the aroma in perfume compositions (EP 0162465).
  • the invention has as its object to propose a new use of saffron and its active ingredients that have numerous qualities and that make it possible to avoid all or part of the above-mentioned drawbacks.
  • the invention has as its object to bring about a sensation of fullness in the overweight person, and even to treat the weight problems effectively without harmful secondary effects on the body, and without the consumer needing to modify his lifestyle or his dietary regimen.
  • the invention relates to the use of saffron and/or its active ingredients: saffron and/or picrocrocin and/or crocin and/or derivatives thereof in the production of an active satiation agent for the management and/or treatment of overweight.
  • the invention also relates to the use of saffron and/or its active ingredients: safranal and/or picrocrocin and/or crocin and/or derivatives thereof in the production of an active satiation agent for the management and/or the treatment of dietary problems, compulsive nibbling cravings linked to stress and/or depression.
  • the invention also has as its object the use of saffron and/or its active ingredients: safranal and/or picrocrocin and/or crocin and/or derivatives thereof for the production of an active satiation agent for the treatment of obesity.
  • Another object of the invention relates to the use of saffron and/or its active ingredients: safranal and/or picrocrocin and/or crocin and/or derivatives thereof for the production of an active satiation agent to help the overweight individual to reduce or control his daily calorie intake and/or to control his body weight and/or his physical appearance.
  • the invention also has as its object the use of saffron and/or its active ingredients: safranal and/or picrocrocin and/or crocin and/or derivatives thereof, in which this or these active ingredient(s) are combined with at least one inert excipient or vehicle, nontoxic, pharmaceutically and/or dietarily acceptable, making it possible to administer it orally.
  • Another object of the invention is the use of saffron and/or its active ingredients: safranal and/or picrocrocin and/or crocin and/or derivatives thereof, in which this or these active ingredient(s) come(s) in the form of a solution or an aqueous suspension in a glass ampoule, in a beverage, in a dropper bottle, in a spray or in the dry state of coated or uncoated tablets, gel capsules, capsules, powders, effervescent tablets, granules, strips, or lozenges.
  • the content of safranal and/or picrocrocin and/or crocin and/or derivatives thereof is selected for an administration of between 0.05 mg/day and 100 mg/day, preferably between 0.2 mg/day and 10 mg/day.
  • the content of safranal and/or picrocrocin and/or crocin and/or derivatives thereof within the satiation agent is between 0.01 and 50%—preferably between 0.05 and 20%, and more particularly between 0.1 and 10%—by weight, relative to the total weight of the satiation agent when the latter is found in solid form or relative to the volume of the satiation agent when the latter is found in liquid form.
  • the active ingredients of saffron are extracted by hydrodistillation followed by liquid/liquid extraction by polar and apolar organic solvents or by a vacuum microwave hydrodistillation (VMHD) or else by an extraction with supercritical CO 2 or with ultrasound, or with ion exchange resins with co-solvents and solvents of polar and/or apolar elution, or else by the set of solid/liquid extraction followed by liquid/liquid extractions.
  • VMHD vacuum microwave hydrodistillation
  • FIG. 1 shows the mean changes in the sensation of hunger before the meal of 16 subjects having either received a placebo treatment for 28 days (group 1 ), or a composition that comprises a saffron stigmata extract according to this invention (group 2 ) between the end (day 28) and the beginning (day 0) of the experiment;
  • FIG. 2 shows the mean changes of the sensation of hunger of group 1 and group 2 at the end of the meal during the experiment from day 0 to day 28;
  • FIG. 3 shows the reduction in body mass by weight, by fat-body mass and by lean-body mass of group 1 and group 2 from day 0 to day 28.
  • saffron such as safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde) of the following formula:
  • picrocrocin (4-(beta-D-glucopyranosyloxy)-2,6,6-trimethyl-1-cyclohexane-1-carboxaldehyde) and crocin (bis(6-O-beta-D-glucopyranosyl-beta-D-glycopyranosyl)8,8′diapo-psi,psi-carotenedioate) of the following formula:
  • BMI body mass index
  • the active ingredients of saffron are extracted from a plant, the Safran Crocus sativus L ., and more particularly stigmata of this plant. It is also possible to extract these active ingredients from other plants, such as Yucca periculosa, Ditaxis heterantha, Cuminum cyminum, Gardenia jasminoides or Camelia Sinensis.
  • the process that is used is known to one skilled in the art. It involves a first hydrodistillation stage, followed next by a second liquid/liquid extraction stage.
  • the hydrodistillation is used to extract the essential oil from the water-immiscible plant.
  • the essence is entrained by the vapor in the form of a heteroazeotrope.
  • the boiling point of the mixture is less than 100°.
  • a mixture of organic substances and water is thus recovered. It is also possible to use pulsed vacuum microwave hydrodistillation (VMHD).
  • VMHD pulsed vacuum microwave hydrodistillation
  • the liquid/liquid extraction is carried out by close contact of the solvent with the solution in equipment that is designed to mix the two phases (ampoules, columns, mixers).
  • the separation of the phases is achieved by gravimetric decanting or centrifuging.
  • the solvents that are used for the extraction are water and ethanol or else ethyl acetate, hexane, petroleum ether, acetone, or methanol.
  • the extraction of safranal, as well as other natural active ingredients of saffron, can also be done using supercritical CO 2 , ideally at 100° C. and 20 MPa.
  • a syrupy liquid product deep garnet red in color with iridescent reflections, is obtained at ambient temperature. It may also come in the form of powder after the water evaporates after, for example, oven-drying or atomization.
  • the satiation agent comprises a content of safranal and/or picrocrocin and/or crocin and/or derivatives thereof between 0.01 and 50%—but preferably a content of between 0.1 and 10%, and more particularly from 1 to 5%—by weight, relative to the total weight of the satiation agent when the latter is in solid or liquid form.
  • satiation agent can be added to the satiation agent, such as bulking agents, fluidizing agents, natural extracts, vitamins, minerals, oligo elements, amino acids, fatty acids, anti-agglomerates, natural oils, aromas, dyes, acidifying agents, thickeners, preservatives and sweeteners.
  • the feedstocks are advantageously microcrystalline cellulose, potato maltodextrin, and magnesium lactate.
  • the thickener that is preferably used is potato starch, hydroxypropylmethyl cellulose, citrus pectin, guar gum, carob, agar-agar, konjac, hydrogenated oils, or beeswax.
  • the fluidizing agents can be magnesium silicate, magnesium stearate, and colloidal silica.
  • the anti-agglomerates are those usually used in the food industry, such as magnesium stearate and colloidal silica.
  • the vitamins are selected from among, i.a., vitamins C, E, B 6 , B 1 , B 2 and B 3 .
  • the natural extracts in addition to the saffron stigmata extract can be extracts from green tea, cinnamon, guarana, Yerba Mate, fennel, queen of the meadow, corn, sage, bee balm, and caffeine.
  • citric acid can be used in the composition of the satiation agent.
  • the stabilizers used in the production of the satiation agent are those usually used in the agricultural industry, such as sorbitol.
  • the aromas that can be used are varied, such as the aroma of coffee, lemon, apple, chocolate, vanilla, and strawberry.
  • the sweeteners that are used are, i.a., xylitol, aspartame, glucose syrup, fructo-oligosaccharide syrup, maltitol in powder or in syrup form, acesulfame potassium, fructo-oligosaccharide, and sodium cyclamate.
  • Fatty acids can also be added to the satiation agent, such as omega 3, omega 6, Galacto, lipids, but also minerals: chromium, boron, magnesium, calcium, iron, molybdenum and amino acids, such as tryptophan, leucine, arginine and glycine.
  • Preservatives are useful so that the satiation agent is preserved over time.
  • the preservatives that are used can be, for example, potassium sorbate, parabenes, sodium benzoate, or ascorbyl palmitate (anti-oxidant).
  • the satiation agent that comprises, i.a., the active ingredients of saffron has the advantage of being easily usable and not restrictive.
  • the content of active ingredients of saffron and more particularly safranal does not need to be very high to achieve the desired effect, i.e., an effect of satiation and therefore a very quick loss of weight of fat-body mass and in the circumference of the waist and hips.
  • the saffron stigmata extract picked up in an ampoule or in a tablet does not have an odor, texture or taste that is disagreeable to the user.
  • the saffron stigmata extract can be combined with other active ingredients, such as vitamins, without this interacting with the effectiveness of the active ingredient.
  • the satiation agent that is thus obtained is stable during its production and its storage.
  • the use of the saffron extract to help the overweight individual reduce or control his daily calorie intake and/or to control his body weight and/or his physical appearance can be done in different ways.
  • this active ingredient can be very simply added to any commonly consumed food (beverages, prepared meals, . . . ) or else be in the form of a dietary addition, dietary products, a medical device, or medications.
  • the concentration of saffron stigmata extract within the medication will be increased so that the satiation effect is felt more strongly.
  • a dose of saffron stigmata extract ranging from 60 to 150 mg per medication will be suitable in particular for persons suffering from the disease of obesity.
  • Ingredient/Tablet Acidifying agent citric acid (E330) 1070.00 Sodium bicarbonate 727.000 Saffron stigmata extract >2% safranal 60.000 20-30% catechin green tea leaf extract 220.000 Stabilizing agent: sorbitol 146.000 Vitamin C 72.000 12% guarana caffeine extract 70.000 Green lemon powder aroma 70.000 8% yerba-mate caffeine extract 42.500 Sweetener: aspartame 30.000 Yellow dye: tartrazine (E102) 0.210 Chromium chloride (19% chromium) 0.025 TOTAL 2507.735
  • the effectiveness of the satiation agent that contains safranal has been tested on a panel of four persons for a duration of 20 days. These four persons have in no way modified their dietary habits nor their lifestyle during the period of the experiment. They have ingested 30 mg of saffron extract in a single dose daily at breakfast.
  • a second clinical study was conducted so as to demonstrate the satiating effect of the active ingredients of saffron in 16 female subjects suffering from compulsive nibbling.
  • the study was conducted over a period of four weeks.
  • the healthy women were slightly overweight, i.e., a BMI of between 22 and 30.
  • a randomization method was implemented so as to divide these 16 subjects into two groups of 8.
  • a first group (group 1 ) took 2 placebo gel capsules each morning and mid-day, while the second group (group 2 ) took two gel capsules/day, also in the morning and at mid-day, of a composition containing a saffron stigmata extract, whereby the two groups each received dietary counseling.
  • composition that contains a saffron extract that was tested on group 2 comprised, i.a., gel capsules of 267 mg+/ ⁇ 10%; 90 mg of saffron stigmata extract stabilized on a microcrystalline cellulose substrate, and colloidal silica; and fatty acids rich in safranal, crocin and picrocrocin; 100 mg of maltodextrin; and 2 mg of magnesium stearate. More particularly, each gel capsule contained 0.9% picrocrocin (or 2.40 mg/gel capsule), 0.4% safranal (or 1.07 mg/gel capsule), and 0.3% crocin (or 0.80 mg/gel capsule).
  • FIG. 1 which shows the demonstration of the sensation of hunger before meals between day 28 and day 0—illustrates, the subjects of group 2 felt a greater reduction of the sensation of hunger before lunch, continuing until dinner, while group 1 (placebo) felt an increase in the sensation of hunger.
  • group 2 has not felt a sensation of hunger at the end of the meal (no variations), while group 1 (placebo) felt an increase from day 0 to day 28.
  • FIG. 3 which shows the reduction in body mass from day 0 to day 28, after 28 days of treatment of 2 gel capsules per day, one in the morning and one at mid-day, a loss of weight on average of ⁇ 1.28 kg was noted in group 2 relative to a loss of weight on average of ⁇ 0.50 kg within group 1 ; a loss of fat-body mass on average of ⁇ 1.28 kg in group 2 relative to the placebo group 1 of ⁇ 0.17 kg; and a loss of lean-body mass of 0 kg within group 2 relative to the placebo group that lost on average ⁇ 0.33 kg.
  • the reduction of the food intake in group 2 is thus connected to an increase in the sensation of fullness that, in contrast to the cognitive restriction, does not induce a sensation of frustration that increases the risk for regaining weight.
  • reducing the sensation of restriction could improve compliance with the regimen and associated loss of weight, as well as to reduce the risk of rebound, often linked to a slackening following the regimen period.

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US12/298,242 2006-04-25 2007-04-23 Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a sateity agent for treatment of obesity Abandoned US20100028464A1 (en)

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Application Number Priority Date Filing Date Title
FR0651443A FR2900053B1 (fr) 2006-04-25 2006-04-25 Utilisation du safranal, de la crocine, de la picrocrocine et leurs derives en tant qu'agent de satiete pour le traitement de la surcharge ponderale
FR0651443 2006-04-25
PCT/FR2007/051158 WO2007125243A1 (fr) 2006-04-25 2007-04-23 Utilisation du safran et/ou du safranal et/ou de la crocine et/ou de la picrocrocine et/ou de leurs derives en tant qu'agent de satiete pour le traitement de la surcharge ponderale

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US13/156,984 Active US9833489B2 (en) 2006-04-25 2011-06-09 Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a sateity agent for treatment of obesity
US15/805,815 Abandoned US20180104299A1 (en) 2006-04-25 2017-11-07 Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a satiation agent for the treatment of obesity

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US15/805,815 Abandoned US20180104299A1 (en) 2006-04-25 2017-11-07 Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a satiation agent for the treatment of obesity

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US20150017278A1 (en) * 2013-07-09 2015-01-15 Carlton R. Branker Method for weight loss and management and herbal composition for achieving the same
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JP6093425B2 (ja) 2017-03-08
FR2900053A1 (fr) 2007-10-26
FR2900053B1 (fr) 2012-11-16
ES2616128T3 (es) 2017-06-09
US20110236481A1 (en) 2011-09-29
JP2016053062A (ja) 2016-04-14
EP2010012B1 (fr) 2016-11-30
JP2009534452A (ja) 2009-09-24
PT2010012T (pt) 2017-02-22
CA2648985C (fr) 2012-06-19
JP2014015480A (ja) 2014-01-30
US20180104299A1 (en) 2018-04-19
EP2010012A1 (fr) 2009-01-07
PL2010012T3 (pl) 2017-07-31
WO2007125243A1 (fr) 2007-11-08
HUE031843T2 (en) 2017-08-28
CA2648985A1 (fr) 2007-11-08
AU2007245501A1 (en) 2007-11-08
US9833489B2 (en) 2017-12-05
DK2010012T3 (en) 2017-03-06

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