WO2007112963A1 - Novel use of ascorbigen - Google Patents

Novel use of ascorbigen Download PDF

Info

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
Authority
WO
WIPO (PCT)
Prior art keywords
mammal
ascorbigen
composition
vitamins
enzymes
Prior art date
Application number
PCT/EP2007/002857
Other languages
French (fr)
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/en

Links

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.

Landscapes

  • 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

Use of ascorbigen to promote the wellness state of a mammal.

Description

Novel use of Ascorbiqen
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. By systematic nomenclature, ascorbigen is a mixture of 2-C(1 H-indol-3-ylmethyl)-α-L-lyxo-3- hexulofuranosonic acid γ-lactone and 2-C(1 H-indol-3-ylmethyl)-α-L-xylo-3- hexulofuranosonic acid γ-lactone. As used herein, the term "ascorbigen" comprises the particular enantiomeres each individually as well as the above mentioned mixture and (stereo-) isomers and mixtures thereof.
Detoxification ("detox") 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.
Malfunctioning as well as overcharging of the detox systems can lead to accumulation of noxious compounds with deleterious effects on health. In this case detoxification can be achieved e.g. artificially by techniques such as dialysis.
Detoxification can be measured by determining one or more of the following parameters:
> Body fluids, hair, and/or tissues analysis for specific compounds (metals, metabolites, drugs)
> Quantification of body weight and/or body mass index
> External skin analysis
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.
The body's own defense system consists on a family of enzymes, so called phase Il enzymes, which neutralize free radicals and convert other toxic compounds in less reactive molecules. In this process, phase Il enzymes, attach "neutralizing" elements to the unwanted substances making them easier for the body to excrete. Examples of 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.
The 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
> lsoprostane tissues level
> 1. 8 - hydroxydeoxyguanosine (8-OhdG) in urine
> Oxidized lipoprotein (LDL) in plasma
> Urine total alkenals and creatinine > Exhaled 8-isoprostane (lung)
A large body of evidence indicates that oxidative stress and other toxic chemical insults support pathological findings, such as e.g. degenerative processes and/or age related diseases. Reducing the formation of toxic reactive species or stimulating their detoxification is therefore essential to create and maintain wellness of the organism involved. Wellness denotes the general state of physical and mental health of an organism, especially when maintained by proper diet, exercise and habits (see The American Heritage® Stedman's Medical Dictionary, publ. Houghton Mifflin Co1 2002). However, the pre-conditions for maintaining the wellness state are not always fulfilled in today's population. The term "wellness state" as used herein denotes to the actual state of physical and mental health of an individual and may therefore vary from being completely healthy to being completely ill and can accordingly be promoted any time when it differs from being completely healthy.
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.
Thus, in one aspect, 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. Such promotion of the wellness state is especially desirable in the status of convalescence, i.e. during recovery of health and strength after illness.
In another aspect, 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.
Furthermore the present invention relates to the use of ascorbigen
> to support the detoxification of a mammal's body;
> to improve the cellular health of an organism;
> to hinder and/or reduce oxidative stress of a mammal's body; and/or
> to boost "antioxidant" vitamins, especially vitamins A, C and E, in their function as free radical scavengers in a mammal's body.
A further object of the present invention is the use of ascorbigen for the manufacture of a composition for
> supporting the detoxification of a mammal's body; > improving the cellular health of an organism;
> hindering and/or reducing oxidative stress; and/or > boosting "antioxidant" vitamins, especially vitamins A, C and E1 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. In fact, 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.
In a further aspect, 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.
While for the purpose of the present invention 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.
For the purposes of the invention, 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. In a particular embodiment of the invention, 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. If administered in a food or beverage 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. If ascorbigen is administered as a pharmaceutical formulation such formulation may contain up to about 500 mg per solid dosage unit, e.g. per capsule. The term "serving" as used herein 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.
The composition according to the present invention can preferably be a nutraceutical composition. The term "nutraceutical" as used herein denotes usefulness in both, the nutritional and pharmaceutical field of application. Thus, "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. In a preferred embodiment of the present invention 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.
By "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. In general, 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. One simple example for a "near water drink" is a mixture of water with very little juice.
If the composition is prepared in form of one of the following food articles it is according to the present invention advantageous if the amount of ascorbigen in the composition is selected from the ranges given in the following table:
Figure imgf000007_0001
If the composition is prepared in form of a capsule it is according to the present invention advantageous if the amount of ascorbigen is selected from the ranges given in the following table:
Figure imgf000008_0001
The invention is further illustrated by Figures 1 to 5:
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. p< 0.05 O Control (untreated) t Paraquat 500μM t Paraquat 500μM + ascorbigen 100μM
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. p< 0.05
O Control (untreated)
▲ N:QO1 (ascorbigen) | UDP-Glucuronosyltransferase (ascorbigen)
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
0 Control (untreated) A N:QO1 (ascorbigen)
1 UDP-Glucuronosyltransferase (ascorbigen)
The invention is further illustrated by the following examples. Examples:
The efficacy of ascorbigen in the selective activation of phase Il enzymes in vitro and in vivo was demonstrated as shown by tests set forth below.
In vitro test model
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.
Results
Compared to control cells (no treatment), cells stimulated with increasing amount of ascorbigen show a dose-dependent increase of NQ01 transcriptional activity (Figure 1 ). These results are also confirmed at the enzymatic level with a significant increase of NQO1 activity (Figure 2).
In vivo test model Male Wistar rats weighing 200 - 220 g, after 4 days of labor acclimation were randomized into groups of 10 animals. Following treatment groups have been analyzed i) Control animals receiving placebo, ii) Test animals receiving 5mg/rat/day of Ascorbigen. The compound was administrated daily by gavages for 7 consecutive days. Food and water were given ad libitum during the experiment. The activation of phase Il enzymes was measured as following:
Livers were collected; RNA and cellular microsomes were fractionated, isolated and stored at -80cC. 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.
Results
Compared to control animals (placebo), rats daily supplemented with Ascorbigen, showed a significant increase in liver's mRNA expression of NADPH:Quinone Oxidoreductase 1 and Glutathione-S-Transferase (figure 4). These results were subsequently confirmed by appropriate enzymatic assays. Both phase Il enzymes showed a significant increase in their enzymatic activities (figure 5). Pharmaceutical compositions may be prepared by conventional formulation procedures.
Example 1 Soft gelatin capsule
Soft gelatin capsules are prepared by conventional procedures containing as active ingredient 100 mg of ascorbigen per capsule.
Example 2
Hard gelatin capsule
Hard gelatin capsules are prepared by conventional procedures containing as active ingredient 100 mg of ascorbigen per capsule.
Example 3
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.

Claims

Claims:
1. Use of ascorbigen to promote the wellness state of a mammal.
2. Use of ascorbigen
• to support the detoxification of a mammal's body;
• to improve the cellular health of an organism;
• to hinder and/or reduce oxidative stress of a mammal's body; and/or
• to boost antioxidant vitamins in their function as free radical scavengers in a mammal's body.
3. Use of Ascorbigen to activate the body's own defence system of a mammal.
4. Use of ascorbigen to selectively activate Phase Il enzymes.
5. The use of ascorbigen in the manufacture of a composition for promoting the wellness state of a mammal.
6. The use of ascorbigen for the manufacture of a composition for • supporting the detoxification of a mammal's body;
• improving the cellular health of an organism;
• hindering and/or reducing oxidative stress of a mammal's body; and/or
• boosting "antioxidant" vitamins in their function as free radical scavengers in a mammal's body.
7. The use of ascorbigen for the manufacture of a composition for the activation of the body's own defence system of a mammal.
8. The use of ascorbigen for the manufacture of a composition for the selective activation of Phase Il enzymes in a mammalian organism.
9. Use according to any of the claims 4 to 8 wherein the composition is a nutraceutical composition.
10. Use according to any of the claims 4 to 8 wherein the composition is a food or beverage or supplement to food or beverage.
11. Use according to any of the claims 9 or 10 wherein the amount of ascorbigen present in the composition is appropriate to provide a dosage of 10 to 1000 mg per day for an adult in one or several dosage units or servings.
12. A method for promoting the wellness state of a mammal by administering a mammal in need of such treatment an effective amount of ascorbigen.
13. A method for selectively activating Phase Il enzymes in a mammal, which comprises administering to a mammal in need of such treatment an effective amount of ascorbigen.
14. A method for
• supporting the detoxification of a mammal's body; • • improving the cellular health of an organism;
• hindering and/or reducing oxidative stress of a mammal's body; and/or
• boosting "antioxidant" vitamins in their function as free radical scavengers in a mammal's body, which comprises administering to a mammal in need of such treatment an effective amount of ascorbigen.
15. A method for the activation of the body's own defence system of a mammal, which comprises administering to a mammal in need of such treatment an effective amount of ascorbigen.
16. The method according to any of the claims 12 to 15 wherein the amount of ascorbigen is appropriate to provide a dosage of 10 to 1000 mg per day for an adult.
PCT/EP2007/002857 2006-03-31 2007-03-30 Novel use of ascorbigen WO2007112963A1 (en)

Applications Claiming Priority (2)

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

Publications (1)

Publication Number Publication Date
WO2007112963A1 true WO2007112963A1 (en) 2007-10-11

Family

ID=38091712

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/EP2007/002857 WO2007112963A1 (en) 2006-03-31 2007-03-30 Novel use of ascorbigen
PCT/EP2007/002858 WO2007112964A1 (en) 2006-03-31 2007-03-30 Novel use of ascorbigen

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/002858 WO2007112964A1 (en) 2006-03-31 2007-03-30 Novel use of ascorbigen

Country Status (1)

Country Link
WO (2) WO2007112963A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107929696B (en) * 2017-12-14 2020-10-23 薛建民 External traditional Chinese medicine composition for relieving swelling, relaxing muscles and setting bones as well as preparation method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017768A1 (en) * 1997-10-08 1999-04-15 Designed Nutritional Products, Inc. Treatment of fibromyalgia and related disorders
RU2235543C1 (en) * 2003-01-28 2004-09-10 Государственное учреждение Научно-исследовательский институт по изысканию новых антибиотиков им. Г.Ф. Гаузе Method for increasing inspecific body resistance

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10308298A1 (en) * 2003-02-26 2004-09-09 Kullmer, Thomas, Priv. Doz. Dr. med. Production of a plant preparation useful for treating cancer comprises extracting glucosinolates from plant material and enzymatically hydrolyzing the glucosinolates to isothiocyanates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017768A1 (en) * 1997-10-08 1999-04-15 Designed Nutritional Products, Inc. Treatment of fibromyalgia and related disorders
RU2235543C1 (en) * 2003-01-28 2004-09-10 Государственное учреждение Научно-исследовательский институт по изысканию новых антибиотиков им. Г.Ф. Гаузе Method for increasing inspecific body resistance

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 *

Also Published As

Publication number Publication date
WO2007112964A1 (en) 2007-10-11

Similar Documents

Publication Publication Date Title
US6368617B1 (en) Dietary supplement
US9446006B2 (en) Hydroxytyrosol combinations for enhancing mitochondrial function and energy production
US20030143311A1 (en) Recovery drink formula and method
AU2011354301B9 (en) Refreshing beverage
CN103520179B (en) Hyperlipidemia improving agent, anemia improve compositions, uric acid level reduces compositions and beverage/food
EP2719379A1 (en) Hydroxytyrosol benefits mitochondria
US20040014692A1 (en) Compositions incorporating(-)-hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors
MXPA06012791A (en) Nutritional composition for increasing creatine uptake in skeletal muscle.
CN101484158A (en) Senescence inhibitor
CN101248873A (en) Drinking food product with sight protection function
CN112739222A (en) Anti-aging agent and anti-aging method
WO2019053580A1 (en) Energy drink composition
CN102753183A (en) Agent for improving motility function
US20030104107A1 (en) Energy drink formula and method
WO2006135084A1 (en) Prophylactic or therapeutic agent for steatohepatitis or fatty liver
WO2007112963A1 (en) Novel use of ascorbigen
RU2776298C1 (en) Biologically active food additives based on ascorbic acid and stevia extract
JP2009533433A (en) Compositions containing pyruvate alkyl esters and uses thereof
Jani Changes in the Regulation of Energy Metabolism with Aging Nutraceutical Applications
KR20060016627A (en) Health food comprising extracts of rhynchosia volubilis as active ingredients for prevention or treatment of osteoporosis
JP2009007256A (en) Nadh/nadph oxidase inhibitor
WO2008152624A2 (en) Herbal energy-enhancing formulation
AU2007202775A1 (en) Compositions incorporating (-)- hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07723799

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07723799

Country of ref document: EP

Kind code of ref document: A1