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WO2019002499A1 - Composition comestible - Google Patents

Composition comestible Download PDF

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Publication number
WO2019002499A1
WO2019002499A1 PCT/EP2018/067476 EP2018067476W WO2019002499A1 WO 2019002499 A1 WO2019002499 A1 WO 2019002499A1 EP 2018067476 W EP2018067476 W EP 2018067476W WO 2019002499 A1 WO2019002499 A1 WO 2019002499A1
Authority
WO
WIPO (PCT)
Prior art keywords
fructose
edible composition
phloretin
eucalyptol
uptake
Prior art date
Application number
PCT/EP2018/067476
Other languages
English (en)
Inventor
Mark John Berry
Mark Ian FOWLER
Alan David HEATH
Original Assignee
Unilever Plc
Unilever N.V.
Conopco, Inc., D/B/A Unilever
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Unilever Plc, Unilever N.V., Conopco, Inc., D/B/A Unilever filed Critical Unilever Plc
Publication of WO2019002499A1 publication Critical patent/WO2019002499A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value

Definitions

  • the present invention relates to an edible composition capable of reducing fructose uptake.
  • Fructose or fruit sugar
  • Fructose is a simple ketonic monosaccharide found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Pure, dry fructose is a very sweet, white, odorless, crystalline solid and is the most water-soluble of all the sugars. Fructose is found in honey, tree and vine fruits, flowers, berries, and most root vegetables. Commercially, fructose is frequently derived from sugar cane, sugar beets, and maize. Crystalline fructose is the monosaccharide, dried, ground, and of high purity.
  • High- fructose corn syrup is a mixture of glucose and fructose as monosaccharides.
  • Sucrose is a compound with one molecule of glucose covalently linked to one molecule of fructose. All forms of fructose, including fruits and juices, are commonly added to foods and drinks for palatability and taste enhancement, and for browning of some foods, such as baked goods.
  • fructose is a cause of insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic syndrome, type 2 diabetes and cardiovascular disease.
  • the European Food Safety Authority has stated that fructose noted that "high intakes of fructose may lead to metabolic complications such as dyslipidaemia, insulin resistance and increased visceral adiposity".
  • Eating fructose causes a post-prandial spike in fructose levels and while the body is able to cope with a certain level of fructose, above this level deleterious effects such as those listed may occur. It is therefore desirable to "flatten the fructose spike" in order to bring fructose down to the level that the body can cope with such that the deleterious effects are prevented. In essence, what is required is that the uptake of fructose is slowed. There is therefore a need for compositions that provide such an effect.
  • US 20140128585 discloses a fructose absorption inhibitor comprising a hydrolyzable tannin as an active component.
  • WO12008474 discloses a fructose absorption inhibitor that has a monoterpene as the active ingredient, and a preventative or therapeutic agent that is for symptoms or maladies caused by overconsumption of fructose.
  • the present invention provides an edible composition comprising from 100 to 500mg of the glucose inhibitor Phloretin and 100-500mg of Eucalyptol .
  • the edible composition comprises from 125 to 450mg of Phloretin, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the edible composition comprises from 125 to 450mg of Eucalyptol , more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the molar ratio of Phloretin to Eucalyptol is in the range 4:1 to 1 :4, preferably 3:1 to 1 :3, most preferably 2:1 to 1 :2, even more preferably 1 .5:1 to 1 :1 .5, most preferably 1.25:1 to 1 :1.25.
  • the edible composition comprises up to 75 wt% fructose, more preferably up to 50 wt% fructose, even more preferably up to 40 wt% fructose, yet more preferably up to 30 wt% fructose, more preferably still up to 20 wt% fructose.
  • the edible composition comprises at least 1 wt% fructose, more preferably at least 2 wt% fructose, even more preferably at least 5 wt% fructose, yet more preferably at least 10 wt% fructose, more preferably still at least 15 wt% fructose.
  • the edible composition is a frozen confection such as an ice cream, or a beverage.
  • the edible composition may be in the form of a packaged beverage comprising no more than 99.95 wt% water.
  • the edible composition may also be in the form of a dry powder contained in a sachet, the dry powder suitable for addition to a meal.
  • the present invention provides an edible composition comprising from 100 to 500mg of Phloretin and 100-500mg of Eucalyptol or Vanillin or a
  • the edible composition for use in the second aspect comprises from 125 to 450mg of Phloretin, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the edible composition comprises from 125 to 450mg of Eucalyptol or Vanillin or a combination thereof, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the molar ratio of Phloretin to Eucalyptol or Vanillin or a combination thereof is in the range 4:1 to 1 :4, preferably 3:1 to 1 :3, most preferably 2:1 to 1 :2, even more preferably 1.5: 1 to 1 :1.5, most preferably 1.25:1 to 1 :1.25.
  • Fructose absorption occurs in the small intestine via the GLUT-5 (fructose only) transporter, the GLUT2 transporter, for which it competes with glucose and galactose, and potentially a number of GLUT transporters of similar structure.
  • GLUT-5 fructose only
  • GLUT2 transporter for which it competes with glucose and galactose, and potentially a number of GLUT transporters of similar structure.
  • Over-consumption of fructose, inhibition of GLUT2, GLUT5 and other transporters of similar structure by phytochemicals, such as flavonoids, or other issues may result in delivery of unabsorbed fructose into the large intestine, which will cause more water to be drawn into the large intestine through the process of osmosis causing diarrhoea.
  • the excessive fructose becomes a source of nutrients for the gut flora resulting in a higher production of short chain fatty acids, hydrogen, carbon dioxide and other gases due to fermentation.
  • This increase of gas causes gastrointestinal side effects that mimic irritable bowel syndrome. For this reason, it is desirable to slow the uptake of fructose rather than prevention.
  • fructose consumption has also been hypothesized to be a cause of insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic syndrome.
  • fructose consumption was correlated with obesity and encouraged visceral adipose tissue deposition in humans.
  • fructose and sucrose produced significantly higher fasting plasma triglyceride values than did the glucose diet in men" and "...if plasma triacylglycerols are a risk factor for cardiovascular disease, then diets high in fructose may be undesirable".
  • Excessive fructose consumption may also contribute to the development of non-alcoholic fatty liver disease.
  • a 2008 study found a risk of incident gout associated with high consumption of fructose or fructose-rich foods. Compared with consumption of high glucose beverages, drinking high-fructose beverages with meals results in lower circulating insulin and leptin levels, and higher ghrelin levels after the meal. Since leptin and insulin decrease appetite and ghrelin increases appetite, some researchers suspect that eating large amounts of fructose increases the likelihood of weight gain.
  • the present invention has surprisingly found that an edible composition with specific combinations of fructose inhibitors Eucalyptol or Vanillin with glucose inhibitor Phloretin is capable of retarding the uptake of fructose.
  • Phloretin is a dihydrochalcone having the following structure:
  • Eucalyptol is a natural organic compound known by a variety of synonyms: 1 ,8-cineol, 1 ,8-cineole, cajeputol, 1 ,8-epoxy-p-menthane, 1 ,8-oxido-p-menthane, eucalyptol, eucalyptole, 1 ,3,3-trimethyl-2-oxabicyclo[2,2,2]octane, cineol, and cineole with the following structure:
  • Vanillin is a phenolic aldehyde with the following structure:
  • Phloretin or Eucalyptol or Vanillin may have an effect on glucose or fructose uptake
  • the combination of Phloretin with Eucalyptol or Phloretin with Vanillin actually provides a synergistic improvement in fructose uptake inhibition. That is to say that the fructose uptake inhibition achieved by Phloretin with Eucalyptol in combination is greater than the inhibition that would be expected merely from the additive effect of these compounds. The same is true for Phloretin with Vanillin.
  • the edible composition of the invention therefore comprises from 100 to 500mg of Phloretin and 100-500mg of Eucalyptol or Vanillin or a combination thereof.
  • the edible composition comprises from 125 to 450mg of Phloretin, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the edible composition comprises from 125 to 450mg of Eucalyptol or Vanillin or a combination thereof, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the molar ratio of Phloretin to Eucalyptol or Vanillin or a combination thereof is in the range 4:1 to 1 :4, preferably 3:1 to 1 :3, most preferably 2:1 to 1 :2, even more preferably 1 .5:1 to 1 :1 .5, most preferably 1 .25:1 to 1 :1.25.
  • the composition itself may comprise high fructose for example up to 75 wt% fructose, more preferably up to 50 wt% fructose, even more preferably up to 40 wt% fructose, yet more preferably up to 30 wt% fructose, more preferably still up to 20 wt% fructose.
  • the edible composition comprises at least 1 wt% fructose, more preferably at least 2 wt% fructose, even more preferably at least 5 wt% fructose, yet more preferably at least 10 wt% fructose, more preferably still at least 15 wt% fructose.
  • Any form of edible composition may be suitable for the present invention.
  • the edible composition of the invention could be consumed as a supplement to a high fructose meal to retard fructose uptake.
  • the edible composition of the invention could be comprised as part of another food product.
  • the edible composition is a frozen confection such as an ice cream, or a beverage. It will be appreciated that the edible composition is intended to be consumed completely in a single sitting, i.e. as a single meal or similar in order to deliver the required levels of Phloretin and Eucalyptol and/or Vanillin.
  • the edible composition may also be in the form of a packaged beverage comprising no more than 99.95 % w/w water.
  • the edible composition can be in the form of a dry powder contained in a sachet, the dry powder suitable for addition to a meal.
  • the invention also provides an edible composition comprising from 100 to 500mg of Phloretin and 100-500mg of Eucalyptol or Vanillin or a combination thereof for use in reducing the uptake of fructose.
  • the edible composition for usejn reducing the uptake of fructose can comprise from 125 to 450mg of Phloretin, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the edible composition for use in reducing the uptake of fructose can comprise from 125 to 450mg of Eucalyptol or Vanillin or a combination thereof, more preferably 150 to 400mg, even more preferably 175 to 350mg, yet more preferably 200 to 300mg, more preferably still 225 to 250mg.
  • the molar ratio of Phloretin to Eucalyptol or Vanillin or a combination thereof in the edible composition for use in reducing the uptake of fructose may bejn the range 4:1 to 1 :4, preferably 3:1 to 1 :3, most preferably 2:1 to 1 :2, even more preferably 1.5:1 to 1 :1 .5, most preferably 1.25:1 to 1 :1 .25.
  • the composition is used to reduce post-prandial fructose uptake.
  • the use is for reduction of post-prandial fructose uptake in a non-diabetic person.
  • the invention may also provide a method of reducing post-prandial fructose uptake in a non-diabetic person comprising the steps of:
  • step (a) is simultaneous with, precedes by 0 to 90, preferably 0 to 60 minutes, or follows by 0 to 30 minutes step (b).
  • the invention may provide a method for treating a person in need thereof for type 2 diabetes comprising the steps of:
  • step (b) oral administration of a composition comprising fructose to the person in need thereof; wherein step (a) is simultaneous with, precedes by 0 to 90, preferably 0 to 60 minutes, or follows by 0 to 30 minutes step (b).
  • the invention could provide a composition according to the first aspect of the invention for use in the treatment of dyslipidaemia, insulin resistance, increased visceral adiposity, or type 2 diabetes.
  • Caco-2 cells were seeded into cell culture inserts (2.5x105 cells/ well for 24 well plates and 1 x105 for
  • DMEM+Glutamax-1 (contains 4.5g/L D-Glucose
  • Lucifer yellow transport as a measure of monolayer integrity and insert membrane integrity was measured by addition Lucifer yellow [Sigma L0144].
  • the cell inserts were transferred to a new plate, the supernatant gently aspirated from the cells and replaced with 100uM Lucifer Yellow solution, PBS(+) added to the collection well and incubated at 37oC 5% C02 for 1 hr. Permeability of the membranes to Lucifer Yellow was checked by measuring the fluorescence of the samples at 485 excitation & 530 emission.
  • the fructose and glucose assay was based on Campbell et al. (1999) "Cost-effective colorimetric microtitre plate enzymatic assays for sucrose, glucose and fructose in sugarcane tissue extracts", J Sci Food Agric 79: 232-236.
  • Glucose and fructose were first converted to glucose-6-phosphate and fructose-6- phosphate respectively in the presence of 1.25mg/ml ATP (Sigma, A26209) and 1 .6U/m Ihexokinase (Sigma, H6380).
  • Glucose-6-phosphate was converted to NADH in the presence of 0.54mg/ml NAD+ (Sigma, N6522) and 0.72U/ml glucose-6-phosphate dehydrogenase (Sigma, G8529) in the same reaction mix.
  • phytonutrients 14 phytonutrients were tested for their ability to inhibit fructose uptake using the model described above. These phytonutrients were:
  • gallic acid ellagic acid; pyrogalol; astilbin; quercetin-3-glucoside; cinnamaldehyde; eucalyptol; vanillin; lectin glycine; aribinogalactan; phloretin; luteolin; phloridzin; luteolin-7-glucoside.
  • DMSO DMSO was deemed to be a notional 100% and so if a test compound, or pair of test compounds, caused a fructose uptake of greater than 100% this was an increase in fructose uptake, and if a test compound, or pair of test compounds caused a fructose uptake of less than 100% this was a decrease in fructose uptake.
  • Table 2 The results are shown in Table 2 in which:
  • Fructose uptake is shown as a percent fructose uptake vs the DMSO control
  • the Glucose Inhibitor is shown by "(G)"
  • the Fructose Inhibitor is shown by "(F)"

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  • Life Sciences & Earth Sciences (AREA)
  • Mycology (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Botany (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition comestible comprenant de 100 à 500 mg de phlorétine et de 100 à 500 mg d'eucalyptol. L'invention concerne également une composition comestible comprenant de 100 à 500 mg de phlorétine et de 100 à 500 mg d'eucalyptol ou de vanilline ou une combinaison de ces éléments et destinée à être utilisée dans la réduction de l'absorption du fructose.
PCT/EP2018/067476 2017-06-30 2018-06-28 Composition comestible WO2019002499A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP17179155 2017-06-30
EP17179146 2017-06-30
EP17179154 2017-06-30
EP17179155.1 2017-06-30
EP17179146.0 2017-06-30
EP17179154.4 2017-06-30

Publications (1)

Publication Number Publication Date
WO2019002499A1 true WO2019002499A1 (fr) 2019-01-03

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PCT/EP2018/067475 WO2019002498A1 (fr) 2017-06-30 2018-06-28 Composition comestible
PCT/EP2018/067476 WO2019002499A1 (fr) 2017-06-30 2018-06-28 Composition comestible
PCT/EP2018/067477 WO2019002500A1 (fr) 2017-06-30 2018-06-28 Composition comestible

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080305052A1 (en) * 2005-07-27 2008-12-11 Symrise Gmbh & Co. Kg. Use of Hesperetin for Enhancing the Sweet Taste
US20100233102A1 (en) * 2006-03-22 2010-09-16 Symrise Gmbh & Co. Kg Use of 4-hydroxydihydrochalcones and their salts for enhancing an impression of sweetness
WO2012008474A1 (fr) 2010-07-14 2012-01-19 富田製薬株式会社 Inhibiteur d'absorption de fructose
US20140107052A1 (en) * 2011-06-06 2014-04-17 Mark John Berry Edible composition
US20140128585A1 (en) 2011-07-07 2014-05-08 Nagaoka Perfumery Co., Ltd. Fructose absorption inhibitor
US20140170083A1 (en) * 2011-06-01 2014-06-19 Symrise Ag Orally consumable formulations comprising certain sweet-tasting triterpenes and triterpene glycosides
KR20160025275A (ko) * 2014-08-27 2016-03-08 대상 주식회사 과당 흡수 억제용 조성물 및 과당 흡수 억제 방법

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080305052A1 (en) * 2005-07-27 2008-12-11 Symrise Gmbh & Co. Kg. Use of Hesperetin for Enhancing the Sweet Taste
US20100233102A1 (en) * 2006-03-22 2010-09-16 Symrise Gmbh & Co. Kg Use of 4-hydroxydihydrochalcones and their salts for enhancing an impression of sweetness
WO2012008474A1 (fr) 2010-07-14 2012-01-19 富田製薬株式会社 Inhibiteur d'absorption de fructose
US20140170083A1 (en) * 2011-06-01 2014-06-19 Symrise Ag Orally consumable formulations comprising certain sweet-tasting triterpenes and triterpene glycosides
US20140107052A1 (en) * 2011-06-06 2014-04-17 Mark John Berry Edible composition
US20140128585A1 (en) 2011-07-07 2014-05-08 Nagaoka Perfumery Co., Ltd. Fructose absorption inhibitor
KR20160025275A (ko) * 2014-08-27 2016-03-08 대상 주식회사 과당 흡수 억제용 조성물 및 과당 흡수 억제 방법

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BAISHAKHI DEY ET AL: "Chemo-profiling of eucalyptus and study of its hypoglycemic potential INTRODUCTION", WORLD J DIABETES, 1 January 2013 (2013-01-01), pages 170 - 176, XP055425279, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797882/pdf/WJD-4-170.pdf> [retrieved on 20171115], DOI: 10.4239/wjd.v4.i5.170 *
CAMPBELL ET AL.: "Cost-effective colorimetric microtitre plate enzymatic assays for sucrose, glucose and fructose in sugarcane tissue extracts", J SCI FOOD AGRIC, vol. 79, 1999, pages 232 - 236

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Publication number Publication date
WO2019002498A1 (fr) 2019-01-03
WO2019002500A1 (fr) 2019-01-03

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