WO2007112963A1 - Nouvelle utilisation de l'ascorbigène - Google Patents

Nouvelle utilisation de l'ascorbigène Download PDF

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Publication number
WO2007112963A1
WO2007112963A1 PCT/EP2007/002857 EP2007002857W WO2007112963A1 WO 2007112963 A1 WO2007112963 A1 WO 2007112963A1 EP 2007002857 W EP2007002857 W EP 2007002857W WO 2007112963 A1 WO2007112963 A1 WO 2007112963A1
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WO
WIPO (PCT)
Prior art keywords
mammal
ascorbigen
composition
vitamins
enzymes
Prior art date
Application number
PCT/EP2007/002857
Other languages
English (en)
Inventor
Luca Barella
Bernd Mussler
Original Assignee
Dsm Ip Assets B.V.
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 Dsm Ip Assets B.V. filed Critical Dsm Ip Assets B.V.
Publication of WO2007112963A1 publication Critical patent/WO2007112963A1/fr

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Classifications

    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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

  • the present invention relates to a novel use of ascorbigen; in particular it relates to the use of ascorbigen to promote the wellness state of a mammal.
  • Ascorbigen is a known indol derivative which can be isolated from cabbage juice or synthetically prepared from ascorbic acid and 3-hydroxymethylindole.
  • ascorbigen is a mixture of 2-C(1 H-indol-3-ylmethyl)- ⁇ -L-lyxo-3- hexulofuranosonic acid ⁇ -lactone and 2-C(1 H-indol-3-ylmethyl)- ⁇ -L-xylo-3- hexulofuranosonic acid ⁇ -lactone.
  • the term "ascorbigen” comprises the particular enantiomeres each individually as well as the above mentioned mixture and (stereo-) isomers and mixtures thereof.
  • Detoxification in general is the removal of unneeded (toxic) substances from the body. Such substances comprise drugs, heavy metals, toxic food compounds and body's own metabolic wastes. Detoxification is a continuous natural process mainly performed through the action of the liver, intestine and kidneys. In a normal healthy body, the detoxification system ensures that the body detoxifies itself. Methods that assist the body's natural detoxification process include the modification of the diet, fasting, colon cleansing, vitamin therapies, herbal or natural treatment, acupuncture and lymphatic drainage and the like.
  • Detoxification can be measured by determining one or more of the following parameters:
  • CONFIRMATION COPY Oxidative stress is caused by the accumulation of chemically reactive molecules called free radicals. Free radicals damage components of the cells' membranes, proteins or genetic material by "oxidizing" them. Accumulation of such cellular damages has been linked to the onset of a number of chronic diseases.
  • phase Il enzymes which neutralize free radicals and convert other toxic compounds in less reactive molecules.
  • phase Il enzymes attach "neutralizing" elements to the unwanted substances making them easier for the body to excrete.
  • phase Il enzymes are Glutathione S-transferase, NAD(P)H:quinone oxidoreductase 1 , UDP-glucuronosyltransferase, Gamma-glutamate cysteine ligase, and Hemeoxygenase-1 which are known to mediate enzymatic body detoxification and/or to exert antioxidant functions thereby protecting cells from toxic damage.
  • phase Il defense system is mainly active in the organ tissue of mammals. Removal of free radicals and other toxic compounds from the cells significantly improves the cellular health status.
  • An additional defense strategy is based on "free radical-scavenger molecules" such as vitamin C and vitamin E which neutralize free radicals by a direct chemical interaction, but do not activate the body's own defense system.
  • Oxidative stress can be measured by determining one or more of the following parameters: > Quantification of antioxidants level in plasma
  • the wellness state can be determined, inter alias, by evaluating parameters (body functions) such as blood pressure, heart rate, body fat composition, pulmonary function, liver function, brain function and levels of physiologically vital components in body fluids etc. as e.g. disclosed in US patent 5,692,501.
  • body functions such as blood pressure, heart rate, body fat composition, pulmonary function, liver function, brain function and levels of physiologically vital components in body fluids etc. as e.g. disclosed in US patent 5,692,501.
  • the present invention relates to the use of ascorbigen to promote the wellness state of a mammal, and to the use of ascorbigen in the manufacture of a composition such as a food or beverage, or a supplement for food or beverage, for promoting the wellness state of a mammal.
  • a composition such as a food or beverage, or a supplement for food or beverage, for promoting the wellness state of a mammal.
  • Such promotion of the wellness state is especially desirable in the status of convalescence, i.e. during recovery of health and strength after illness.
  • the present invention relates to a method of promoting and/or maintaining the wellness state of a mammal by administering a mammal an effective amount of ascorbigen.
  • a further object of the present invention is the use of ascorbigen for the manufacture of a composition for
  • antioxidant vitamins especially vitamins A, C and E 1 in their function as free radical scavengers in a mammal's body.
  • Vitamins are micronutrients essential for life which participate in a vast variety of biological processes. Some of these, such as vitamins A, C and E, share an additional function as “free radical scavengers", i.e. they also posses the ability to neutralize the highly chemical reactive free radical molecules and can therefore be characterized as the "antioxidant” vitamins. Antioxidant vitamins help preventing the damaging of body's membranes, proteins and DNA. Through this chemical interaction, the free radical is neutralized at the cost of the vitamin destruction.
  • Ascorbigen surprisingly protects the antioxidant vitamins and therefore acts as a vitamin booster.
  • these vitamins by increasing the survival chance of these vitamins, their additional biological actives in the immune system, bone growth and collagen production can be fully exploited (boosted).
  • the vitamin boosting effect can be measured by determining the plasma vitamin status.
  • the invention relates to the use of ascorbigen to selectively activate Phase Il enzymes, to the use of ascorbigen in the manufacture of a composition for the selective activation of Phase Il enzymes in a mammalian organism and to a method of selectively activating Phase Il enzymes in a mammal, which comprises administering to a mammal in need of such treatment an effective amount of ascorbigen.
  • mammals are preferably humans, the invention is not limited to humans but includes other mammals, especially pets such as horses, dogs, cats and/or small animals, e.g. hamsters and/or guinea pigs.
  • ascorbigen may be administered to, e.g., a human adult (weighing about 70 kg) in an amount of up to about 10 to 1000 mg/day in one or several dosage units or servings.
  • the dosage for a human adult (weighing about 70 kg) is up to about 500 mg/day, especially up to about 100 to 200 mg/day.
  • the amount of ascorbigen contained therein is suitably no less than about 50 mg per serving. In another embodiment of the invention such amount is no less than about 100 mg per serving.
  • ascorbigen is administered as a pharmaceutical formulation such formulation may contain up to about 500 mg per solid dosage unit, e.g. per capsule.
  • serving denotes an amount of food and/or beverage normally ingested by a human adult with a meal at a time and may range, e.g., from about 100 g to about 500 g food and/or beverage.
  • composition according to the present invention can preferably be a nutraceutical composition.
  • nutraceutical as used herein denotes usefulness in both, the nutritional and pharmaceutical field of application.
  • “nutraceutical compositions” according to the present invention can serve as supplements to food, feed and beverages, dietary supplements and as pharmaceutical formulations which may be solid - such as capsules - or liquid - such as solutions or suspensions. It is evident from the foregoing that the term “nutraceutical composition” also comprises food, feed and beverages containing ascorbigen.
  • a multi-vitamin and mineral supplement may be added to the compositions according to the present invention, e.g. to maintain a good balanced nutrition or to obtain an adequate amount of an essential nutrient missing in some diets.
  • the multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns and common inadequate dietary patterns sometimes observed in diabetes.
  • the composition according to the present invention can be a food or beverage composition.
  • Beverages can be e.g. sports drinks, energy drinks or other soft drinks, or any other suitable beverage preparation, e.g. joghurt drinks, hot beverages or soups.
  • the beverage is an "instant beverage", i.e. a beverage which is produced - normally by the consumer themself - by stirring a powder into a liquid, usually milk or water.
  • Sports drink a beverage is meant which is consumed before, during and/or after physical exercise, mainly to hydrate as well as to (re-) store electrolytes, sugar and other nutrients. Sports drinks are usually isotonic, meaning they contain the same proportions of nutrients as found in the human body.
  • Energy drinks are beverages which contain (legal) stimulants, vitamins (especially B vitamins) and/or minerals with the intent to give the user a burst of energy.
  • Common ingredients include caffeine, guarana (caffeine from the Guarana plant) and/or taurine, various forms of ginseng, maltodextrin, inositol, carnitine, creatine, glucuronolactone, coenzyme Q10 and/or ginkgo biloba.
  • Some may contain high levels of sugar, or glucose, whereas others are sweetened completely or partially with a sugar alcohol and/or an artificial sweetener like Ca-cyclamate or Aspartame. Many such beverages are flavored and/or colored.
  • a soft drink is a drink that does not contain alcohol.
  • the term is used only for cold beverages. Hot chocolate, tea, and coffee are not considered soft drinks.
  • the term includes carbonated and non-carbonated drinks, e.g. mineral water or so-called “near water drinks", i.e. water-based beverages which have an additional benefit, e.g. a special flavor and/or further (functional) ingredients.
  • a "near water drink” is a mixture of water with very little juice.
  • Figure 1 shows the effect of ascorbigen stimulation on NADPH: Quinone oxidoreductase (NADPH:QO1 ) RNA expression in HepG2 cells.
  • the y-axis shows the fold induction. Data are average out of 3 independent experiments. * p ⁇ 0.05.
  • Figure 2 shows the effect of ascorbigen stimulation on NADPH: Quinone oxidoreductase (NADPH:QO1 ) enzymatic activity in HepG2 cells.
  • the y-axis shows the induction in %. Data are average out of 3 independent experiments. * p ⁇ 0.05.
  • Figure 3 shows the effect of ascorbigen against free radical challenge (Paraquat) on HepG2 cells survival.
  • the y-axis shows the survival rate in %. Data are average out of 3 independent experiments.
  • Figure 4 shows the effect of ascorbigen supplementation on RNA expression of NADPH: Quinone oxidoreductase 1 (N:QO1 ) and UDP-Glucuronosyltransferase in rat liver.
  • the y-axis shows the fold induction.
  • Figure 5 shows the effect of ascorbigen supplementation on NADPH: Quinone oxidoreductase 1 (N:QO1 ) and UDP-Glucuronosyltransferase enzymatic activity in rat liver.
  • the y-axis shows the induction rate in %. * p ⁇ 0.05
  • Liver cells HepG2 were treated with physiological amount of ascorbigen in a dose-dependent fashion for 16 hours. Cells were harvested and RNA isolated. The enzyme NAD(P)H:Quinone Oxidoreductasel (NQO1 ) was chosen as a representative for the family of phase Il enzymes. Quantification of NQO1 transcript was performed by real time PCR TaqMan®. Likewise, cells were harvested after stimulation with ascorbigen and the enzymatic activity of NQ01 was measured.
  • RNA and cellular microsomes were fractionated, isolated and stored at -80 c C.
  • Transcriptional activation of the phase Il enzyme representatives NADPH:Quinone Oxidoreductase 1 and Glutathione-S-Transferase was assessed by quantitative PCR. Enzymatic activity was measured based on appropriate assays.
  • compositions may be prepared by conventional formulation procedures.
  • Soft gelatin capsules are prepared by conventional procedures containing as active ingredient 100 mg of ascorbigen per capsule.
  • Hard gelatin capsules are prepared by conventional procedures containing as active ingredient 100 mg of ascorbigen per capsule.
  • Food items may be prepared by conventional procedures containing ascorbigen in an amount of 50 mg to 500 mg per serving.
  • examples of such food items are soft drinks, bread, cookies, yoghurt, ice cream, and sweets.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Mycology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Microbiology (AREA)
  • Nutrition Science (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'invention concerne une utilisation de l'ascorbigène pour promouvoir le bien-être d'un mammifère.
PCT/EP2007/002857 2006-03-31 2007-03-30 Nouvelle utilisation de l'ascorbigène WO2007112963A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP06006814 2006-03-31
EP06006814.5 2006-03-31

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WO2007112963A1 true WO2007112963A1 (fr) 2007-10-11

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PCT/EP2007/002858 WO2007112964A1 (fr) 2006-03-31 2007-03-30 Nouvelle utilisation de l'ascorbigène

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CN107929696B (zh) * 2017-12-14 2020-10-23 薛建民 一种消肿松肌正骨的外用中药组合物及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017768A1 (fr) * 1997-10-08 1999-04-15 Designed Nutritional Products, Inc. Traitement de fibromyalgie et de troubles qui y sont lies
RU2235543C1 (ru) * 2003-01-28 2004-09-10 Государственное учреждение Научно-исследовательский институт по изысканию новых антибиотиков им. Г.Ф. Гаузе Способ повышения неспецифической резистентности организма

Family Cites Families (1)

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Publication number Priority date Publication date Assignee Title
DE10308298A1 (de) * 2003-02-26 2004-09-09 Kullmer, Thomas, Priv. Doz. Dr. med. Verfahren zur Herstellung von Präparationen mit hochkonzentrierten Brassica-Inhaltsstoffen und deren Verwendung

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017768A1 (fr) * 1997-10-08 1999-04-15 Designed Nutritional Products, Inc. Traitement de fibromyalgie et de troubles qui y sont lies
RU2235543C1 (ru) * 2003-01-28 2004-09-10 Государственное учреждение Научно-исследовательский институт по изысканию новых антибиотиков им. Г.Ф. Гаузе Способ повышения неспецифической резистентности организма

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Verwendung von Ascorbigen als Anti-Aging Mittel", IP.COM JOURNAL, IP.COM INC., WEST HENRIETTA, NY, US, 24 February 2005 (2005-02-24), XP013023450, ISSN: 1533-0001 *
DAS SRINIBAS ET AL: "Cancer modulation by glucosinolates: A review", CURRENT SCIENCE (BANGALORE), vol. 79, no. 12, 25 December 2000 (2000-12-25), pages 1665 - 1671, XP002436977, ISSN: 0011-3891 *
PEREVERZEVA E ET AL: "Ascorbigen accelerates small intestine anti-infective barrier function in suckling mice", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, vol. 24, December 2004 (2004-12-01), & 6TH EUROPEAN CONGRESS OF CHEMOTHERAPY AND INFECTION/24TH INTERDISCIPLINARY MEETING ON ANTI-INFECTIOU; PARIS, FRANCE; DECEMBER 01 -03, 2004, pages S233 - S234, XP002436978, ISSN: 0924-8579 *
PREOBRAZHENSKAYA M N ET AL: "Ascorbigen and other indole-derived compounds from Brassica vegetables and their analogs as anticarcinogenic and immunomodulating agents", PHARMACOLOGY AND THERAPEUTICS, vol. 60, no. 2, 1993, pages 301 - 313, XP002436766, ISSN: 0163-7258 *

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