US20090060956A1 - Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity) - Google Patents

Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity) Download PDF

Info

Publication number
US20090060956A1
US20090060956A1 US12/094,648 US9464806A US2009060956A1 US 20090060956 A1 US20090060956 A1 US 20090060956A1 US 9464806 A US9464806 A US 9464806A US 2009060956 A1 US2009060956 A1 US 2009060956A1
Authority
US
United States
Prior art keywords
foodstuff
fructose
enzyme
glucose isomerase
fructose dehydrogenase
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US12/094,648
Other languages
English (en)
Inventor
Daniel Henry Wyrobnik
Isaac Harry Wyrobnik
Elliad Ronen Silcoff
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pro Natura Gesellschaft fuer Gesunde Ernaehrung mbH
Original Assignee
Individual
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
Priority claimed from DE102006013623A external-priority patent/DE102006013623A1/de
Priority claimed from DE102006014420A external-priority patent/DE102006014420A1/de
Application filed by Individual filed Critical Individual
Priority to US12/094,648 priority Critical patent/US20090060956A1/en
Assigned to PRO NATURA GESELLSCHAFT FUR GESUNDE ERNAHRUNG MBH reassignment PRO NATURA GESELLSCHAFT FUR GESUNDE ERNAHRUNG MBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WYROBNIK, DANIEL HENRY, WYROBNIK, ISAAC HARRY, SILCOFF, ELLIAD RONEN
Publication of US20090060956A1 publication Critical patent/US20090060956A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
    • 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
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • 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
    • A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/52—Isomerases (5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/99—Oxidoreductases acting on the CH-OH group of donors (1.1) with other acceptors (1.1.99)
    • C12Y101/99011—Fructose 5-dehydrogenase (1.1.99.11)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y503/00—Intramolecular oxidoreductases (5.3)
    • C12Y503/01—Intramolecular oxidoreductases (5.3) interconverting aldoses and ketoses (5.3.1)
    • C12Y503/01005—Xylose isomerase (5.3.1.5)
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y503/00—Intramolecular oxidoreductases (5.3)
    • C12Y503/01—Intramolecular oxidoreductases (5.3) interconverting aldoses and ketoses (5.3.1)
    • C12Y503/01018—Glucose isomerase (5.3.1.18)

Definitions

  • the present invention relates to an agent for reducing the useable calorie content of food.
  • the agent contains a compound that can effect the conversion of fructose to 5-keto-D-fructose. 5-keto-D-fructose cannot be metabolized by the human or animal body and is therefore significantly less caloric than fructose.
  • the present invention also relates to an agent which, in addition to the first compound, contains a compound that can effect the conversion of glucose to fructose.
  • the term “agent” includes a pharmaceutical composition, a medical device, a foodstuff and a special foodstuff.
  • the terms “food” and “foodstuff” are used as synonyms. They mean to also include feed in the sense of animal feed.
  • special foodstuffs are foodstuffs for particular nutritional uses, foods for special medical purposes, medical foods, food supplements, dietary supplements, dietetic food supplements, health foods, nutraceuticals, and food additives.
  • foodstuff means to include special foodstuffs as used herein, where applicable.
  • Fructose is a ketohexose and is an important energy providing ingredient of food. It is present as a component of many di- and oligosaccharides, as free fructose or as both in numerous foodstuffs. In contrast to glucose, fructose is assimilated into the mucosa cells of the small intestine by eased carrier-mediated diffusion. The enzymatic degradation starts in the liver by the action of the adenosine triphosphate (ATP) dependent fructokinase, whereby fructose is converted to fructose 1-phosphate. In the liver and in the kidneys, fructose 1-phosphate is cleaved to glycerine aldehyde and dihydroxy acetone phosphate by aldolase B.
  • ATP adenosine triphosphate
  • Food e.g. fruits and fruit juices
  • sucrose which is cleaved to fructose and glucose in the body.
  • free fructose which is approx. 1.6-fold sweeter than glucose or sucrose
  • HFCS high fructose corn syrup
  • fructose does not eliminate the appetite, obesity may easily occur as a result of the extensive use of HFCS as a sweetener. Free fructose in large amounts may also favor hypertension. Large amounts of free fructose also influence the lipid profile (blood lipids) in an unfavorable way, since they promote the synthesis of lipids and thus increase the postprandial serum triglycerides. Patients with metabolic syndrome should not consume beverages that are sweetened with HFCS or sucrose. Fructose is also discussed as a cause of metabolic syndrome.
  • fructose is an important source of calories for the human body and must be given special consideration in all efforts to reduce the content of calories in the food.
  • the term “fructose containing” refers to all substances and foodstuffs that either contain fructose in pure form or from which fructose can be released in the digestive tract.
  • the fructose content of substances and foodstuffs refers to all the fructose in a fructose containing food or substance in whatever form (e.g. also as part of sucrose) it is contained in such a food or substance.
  • the individual grades are classified according to the well-known body mass index (BMI).
  • BMI body mass index
  • adiposity grade I to grade III has increased constantly in the industrialized countries over the past decades and amounts to 30 to 50% of the total population at present, depending on the statistic used and definition of the term overweight or obesity. For example, in the Federal Republic of Germany, every second person is overweight (adiposity grade I) and every sixth person has adiposity grade II or III. The number of adipose children is also increasing as a result of poor nutrition and lack of exercise. To date, therapy has been limited to nutrition therapy and, in extreme cases, surgical measures. It is a well-known fact that there is a very large and constantly increasing number of nutrition therapies and diets that generally do not result in lasting success.
  • An agent that does not have an effect on the body, but on the carbohydrates in the food and that would reduce the useable calorie content in the food would satisfy an extremely widespread and pressing need which has existed for decades.
  • Such an agent would also overcome the prejudice widely held in the specialist world and among those suffering from obesity that a lasting weight reduction or the prevention of an increase in weight is not possible without suffering and without a significant change of nutrition habits. It would mean a dramatic improvement in the options available for the treatment of adiposity.
  • Such an agent would also put an end to the as yet fruitless efforts of the specialist world to find an agent to treat adiposity which can be administered broadly, easily, and long-term, without causing side effects. This would apply all the more to an agent which, in addition, has no negative effects on health.
  • an object of the present invention to provide an agent that significantly reduces the useable calorie content of food, in particular for facilitating the intake of foodstuffs that normally contain fructose also in the case of adiposity, without resulting in an increase in weight. Further, it is the object of the invention to make it possible for persons suffering from adiposity to eat foodstuffs which until now were not allowed to them due to their fructose content or the eating of which was associated with negative effects for the sufferers' health. Another objective is to provide an agent that, after the intake of fructose, can reduce or prevent the associated negative effects on weight and/or health, in particular in the case of adiposity.
  • the subject matter of the invention is an agent that can solve all of the problems described above.
  • the agent contains 5-D-fructose dehydrogenase (syn. fructose 5-dehydrogenase).
  • the agent according to the present invention brings about the conversion of fructose in the food into 5-keto-D-fructose by dehydrogenation.
  • the fructose is changed in such a manner that it is no longer available to the metabolism of the human or animal body.
  • 5-D-fructose dehydrogenase is used, optionally in combination with glucose isomerase, for treatment of adiposity, for example in the form of a pharmaceutical composition.
  • adiposity may be therapeutic or prophylactic.
  • further diseases accompanying adiposity may be treated by making use of the agent according to the invention.
  • the agent is used for lowering the usable calorie content of food.
  • a subject matter of the invention is also an agent that reduces the bioavailability of fructose in the human or animal body with the help of a 5-D-fructose dehydrogenase.
  • a subject matter of the invention is also an agent that reduces the bioavailability of fructose and glucose in the human or animal body with the help of a 5-D-fructose dehydrogenase in combination with a glucose isomerase.
  • a subject matter of the invention is also an agent that reduces the content of fructose in a foodstuff with the help of a 5-D-fructose dehydrogenase.
  • a subject matter of the invention is also an agent that reduces the content of fructose and glucose in a foodstuff with the help of a 5-D-fructose dehydrogenase in combination with a glucose isomerase.
  • a subject matter of the present invention is further an agent for reducing the useable calorie content of food which contains a 5-D-fructose dehydrogenase—alone or in combination with a glucose isomerase.
  • the agent according to the invention is suited for the use in the case of adiposity and for the therapeutic or prophylactic treatment of adiposity, possibly accompanied by a further disease usually appearing together with adiposity, including diseases of the cardiovascular system (e.g. hypertension, coronary heart disease, venous insufficiency, heart failure, left-ventricular hypertrophy, arteriosclerosis), of metabolic and hormonal function (e.g. diabetes mellitus type II, dyslipidemias, hyperuricemia, hyperlipoproteinemia), of the respiratory system (e.g. sleep apnea, Pickwickian syndrome), of the hepatobiliary system (e.g.
  • diseases of the cardiovascular system e.g. hypertension, coronary heart disease, venous insufficiency, heart failure, left-ventricular hypertrophy, arteriosclerosis
  • metabolic and hormonal function e.g. diabetes mellitus type II, dyslipidemias, hyperuricemia, hyperlipoproteinemia
  • fatty liver, cholecystolithiasis), of the locomotor system e.g. gonarthrosis, heel spur, arthrosis of the ankle joint
  • the skin e.g. intertrigo, hirsutism, striae
  • neoplasias associated with adiposity e.g. increased risk of endometrial, breast, cervical, gall bladder cancer, etc.
  • disorders of sexual function e.g. reduced fertility, complications during birth
  • psychosocial problems e.g. reduced self-confidence, social isolation, discrimination, problems with one's partner or at work
  • other problems such as reduced mobility and staying power, increased risk during operations and more difficult examination conditions.
  • a further subject matter of the invention is the use of a 5-D-fructose dehydrogenase—alone or in combination with a glucose isomerase—in the case of adiposity or in the case of health problems or diseases associated with adiposity (see above).
  • a further subject matter of the invention is the use of 5-D-fructose dehydrogenase—alone or in combination with a further enzyme, preferably together with glucose isomerase—for the manufacture of a medicament (pharmaceutical composition) for the prophylactic or therapeutic treatment of adiposity or diseases associated with adiposity (see above).
  • a 5-D-fructose dehydrogenase alone or in combination with a glucose isomerase—may also be used for reducing the useable calorie content in a foodstuff.
  • a 5-D-fructose dehydrogenase in the context of this application, is an enzyme that can catalyze the dehydrogenation of fructose to 5-keto-D-fructose.
  • a possible method for the production of a 5-D-fructose dehydrogenase is, for example, described in Ameyama et al., Journal of Bacteriology 1981, 814-823, “D-Fructose Dehydrogenase of Gluconobacter industrius: Purification, Characterization and Application of Enzymatic Microdetermination of D-Fructose”, the content of which is incorporated herein by reference.
  • fructose is used very widely in the foodstuff industry as a sweetener.
  • the content of calories can be reduced by about one half by the use of the agent according to the present invention which contains the enzyme 5-D-fructose dehydrogenase.
  • sucrose is enzymatically cleaved to glucose and fructose.
  • the fructose fraction (50% of the calories contained in sucrose) is then dehydrogenated by said 5-D-fructose dehydrogenase to 5-keto-D-fructose and can therefore no longer be utilized by the body.
  • Glucose is the central carbohydrate of the energy and substrate metabolism. It is the basic component of many polysaccharides (e.g. starch).
  • glucose containing refers to all substances and foodstuffs that either contain glucose in pure form or from which glucose can be released in the digestive tract.
  • the glucose content of substances and foodstuffs refers to all the glucose in a glucose containing food or substance in whatever form (e.g. also as part of sucrose) it is contained in such a food or substance.
  • compositions and methods that can be used to enable sufferers of Adiposity to ingest fructose-containing foods or fructose- and glucose-containing foods
  • a glucose isomerase in the context of this application is an enzyme that is able to transform glucose into fructose. This conversion can also be brought about, for example, by a xylose isomerase. Thus, such a xylose isomerase is, in the context of this application, also a glucose isomerase.
  • a possible method for the production of a xylose isomerase is, for example, described in Yamanaka, Biochimica et Biophysika Acta, Volume 151 (3), 1968, 670-680, “Purification, Crystallization and Properties of the D-Xylose Isomerase from Lactobacillus brevis” and in Yamanaka, Methods in Enzymology, Volume 41, 1971, 466-471, “D-Xylose Isomerase from Lactobacillus brevis”, the contents of which are incorporated herein by reference.
  • Such a combination agent can also be used in the form of two separate dose units, e.g. in two separate tablets, one of which contains glucose isomerase and the other 5-D-fructose dehydrogenase.
  • 5-D-fructose dehydrogenase By combining 5-D-fructose dehydrogenase with the enzyme glucose isomerase, ingested glucose as well as the large amounts of glucose released by the degradation of carbohydrates are largely removed from the metabolism of calories by the body.
  • Glucose isomerase has the property of converting glucose into fructose and vice versa with an equilibrium concentration of approximately 50% glucose and 50% fructose.
  • Such an enzyme combination consisting of 5-D-fructose dehydrogenase and glucose isomerase is ideally suited for considerably reducing the calorie content of, for example starch containing food, such as potatoes.
  • the glucose that is released from starch during digestion is transformed into fructose by said glucose isomerase, which is then converted by said 5-D-fructose dehydrogenase into 5-keto-D-fructose which is significantly less bioavailable.
  • the 5-D-fructose dehydrogenase prevents the above described equilibrium from being established. Therefore, glucose isomerase will convert glucose into fructose, which itself will be dehydrogenated by the 5-D-fructose dehydrogenase to 5-keto-D-fructose, until no further glucose is present in the food and food pulp.
  • the combination agent according to the present invention thus leads to a large proportion of the glucose supplied to the body or released in the digestive tract being converted into fructose which in turn is converted into 5-keto-D-fructose, which is of much less value for the metabolism.
  • the invention facilitates the transformation of fructose in a foodstuff into a form that prevents weight gain and enables weight loss.
  • the invention also facilitates the intake of foodstuffs by persons who suffer from adiposity that had to be avoided by the sufferers up to now because of their content of fructose and glucose.
  • the invention allows the intake of fructose and glucose containing foodstuffs by persons who are not suffering from adiposity, without this leading to negative effects on their weight and/or health.
  • a subject matter of the invention is also a product which consists of 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—or contains 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—beside one or more other active ingredients for use in a medical method, in particular in a method for the therapeutic treatment of the human or animal body.
  • a pharmaceutical composition is a product, in particular a substance or a substance mixture, for use in a method for surgical or therapeutic treatment of the human or animal body and in diagnostic methods that are performed on the human or animal body.
  • pharmaceutical compositions are also products, in particular substances or substance mixtures, that are meant or suitable for curing, alleviating, preventing or determining adiposity.
  • treating when used in connection with the foregoing disorders includes amelioration, prevention or relief from the symptoms and/or effects associated with these disorders and includes the prophylactic administration of an enzyme or a mixture thereof to diminish the likelihood or seriousness of the conditions.
  • a foodstuff which contains 5-D-fructose dehydrogenase—alone or in combination—with glucose isomerase.
  • a foodstuff which contains 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—in an amount which is sufficient to convert fructose into 5-keto-D-fructose and which, in addition, contains glucose isomerase in an amount which is effective for transforming glucose into fructose.
  • Such a foodstuff may be produced using a method for treating a foodstuff in which the foodstuff is placed in contact with a 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—under such conditions under which the 5-D-fructose dehydrogenase can dehydrogenate fructose to 5-keto-D-fructose and under which the glucose isomerase can convert glucose into fructose.
  • a foodstuff In contrast to otherwise untreated foodstuffs, such a foodstuff has a reduced content of fructose or, if the agent contains both enzymes, a reduced content of fructose and glucose, and therefore, for the first time, is suitable to be consumed by persons who want to control their weight, including adipose persons.
  • a foodstuff can be prepared by a method in which a 5-D-fructose dehydrogenase is added to the foodstuff—alone or in combination with glucose isomerase—in a manner in which the action of the enzyme or both enzymes only starts after the intake of the foodstuff.
  • Such a foodstuff that contains 5-D-fructose dehydrogenase or 5-D-fructose dehydrogenase and glucose isomerase has the same taste as an untreated foodstuff and is, for the first time, suitable to be consumed by persons who want to control their weight including adipose persons due to the reduced content of fructose or fructose and glucose which is established after eating.
  • the subject matter of the invention is accordingly also a medical device that consists of 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—or contains the 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—beside one or more other active ingredients.
  • 5-D-Fructose dehydrogenase is a compound that has been known for nearly 40 years, but has only been used for analytical purposes to date.
  • Glucose isomerase is a compound that has been known for more than 40 years and has only been used for starch saccharification to date. In the industry, it is used for the conversion of glucose into fructose as well as for the conversion of fructose into glucose.
  • 5-D-fructose dehydrogenase in particular in combination with glucose isomerase, has not been used in the medical/pharmaceutical field to date, in particular not in adiposity in humans or animals.
  • the invention discloses the first medical indication for 5-D-fructose dehydrogenase and the first medical indication for the combination of the two enzymes.
  • the two enzymes have not been used for the therapeutic treatment of the human or animal body or for diagnostic purposes on the human or animal body.
  • the agent according to the present invention may be taken orally prior to meals, immediately before meals, with meals or immediately after meals, so that it can exert its dehydrogenating effect on fructose and optionally converting effect on glucose in the food pulp.
  • the agent according to the present invention may contain the enzyme(s) without further additives.
  • the agent according to the present invention further contains additives that are pharmaceutically acceptable and/or acceptable for foodstuffs, such as for example extenders, binders, stabilizers, preservatives, flavourings, etc.
  • additives are commonly used and well known for the production of pharmaceutical compositions, medical devices, foodstuffs, and special foodstuffs and the person skilled in the art knows which additives in which amounts are suitable for certain presentation forms.
  • the agents according to the present invention may for example contain as additives dicalcium phosphate, lactose, modified starch, microcrystalline cellulose, maltodextrin and/or fibersol.
  • the agents according to the present invention can also be added to a foodstuff before eating. They may even be added to the foodstuff at the production stage, with the aim of developing their effect only after consuming the foodstuff. This may be achieved by microencapsulation, for example. With this, the useable fructose and/or glucose content of the foodstuff may be reduced, without negatively affecting its taste. Therefore, preparations are particularly useful that contain 5-D-fructose dehydrogenase—alone or in combination with glucose isomerase—and which release these enzymes only in the digestive tract of a human or animal or let them become effective in another way, in particular in the stomach or small intestine. Therefore, the invention can be used for example in the production of sweets, fruit preparations (e.g.
  • apple sauce jam, honey, chocolate and chocolate products, bakery products (e.g. biscuits and cakes), breads, pastas, vegetable dishes, potato dishes, ice cream, cereals, dairy products (e.g. fruit yogurt and pudding), fructose- and/or glucose-containing beverages, fructose- and/or glucose-containing sauces (e.g. tomato ketchup) and fructose- and/or glucose-containing sweeteners.
  • the agents according to the present invention could e.g. be mixed into or sprinkled onto them after cooling.
  • fructose is widely used as a sweetener in foodstuffs that are especially produced for diabetics
  • the addition of the agents according to the present invention to diabetic food before eating or the addition of the agents according to the present invention during the production of diabetic food allows diabetics who suffer from adiposity to eat diabetic food, such as the above mentioned foodstuffs in their respective form as diabetic foods.
  • the agent according to the present invention may also be added to a foodstuff, to exert its effect on the fructose originating from another foodstuff and in the case of an agent containing both enzymes also on the glucose originating from another foodstuff after their consumption.
  • An example of this would be the addition of the agent according to the present invention to a spread so that the reduction of the calories that are contained in the bread and that can be utilized by the body occurs after the intake of the bread, without an impairment of taste of the bread.
  • Another example would be mixed spices and mayonnaise, among other things for use with french fries.
  • 5-D-fructose dehydrogenase and the combination agent may also be used in immobilized form. This is useful for the treatment of liquid foodstuffs.
  • 5-D-fructose dehydrogenase can be embedded in a matrix which is permeable for fructose. If a fructose containing liquid foodstuff is allowed to flow along the enzyme containing matrix, then fructose is extracted from the foodstuff by the action of the enzyme and converted into 5-keto-D-fructose.
  • a subject matter of the present invention are also agents that in addition to other active ingredients also contain 5-D-fructose dehydrogenase, either alone or in combination with glucose isomerase.
  • the agent may be formulated in any form which is suitable for the intended route of administration.
  • a preferred route of administration is oral administration.
  • the agent may be formulated for example in the form of capsules (coated or non-coated) containing powder, coated or non-coated pellets, granules or micro-/mini-tablets or in the form of tablets (coated or non-coated) pressed from powder, coated or non-coated pellets, dragees or micro-/mini-tablets.
  • the agent may also be formulated for example in the form of gel caps or in liquid form as solution, drops, suspension or gel.
  • the agent may also be formulated e.g. as dried or moist oral supplement.
  • the formulation of the agent according to the present invention as powder is particularly suitable for admixing with foodstuff.
  • the powder may be sprinkled onto a meal or mixed into a pulp or beverage. It is particularly beneficial, if the agent offered as bulk powder is packaged in single dosage amounts, such as in single bags or capsules, or if it is provided in a dosing dispenser.
  • the 5-D-fructose dehydrogenase (one or in combination with glucose isomerase—may be used with acceptable excipients and/or carriers.
  • the total amount of the carrier and/or excipient of an agent containing 5-D-fructose dehydrogenase or 5-D-fructose dehydrogenase and glucose isomerase is preferably between 5 and 99.9% by weight, more preferably between 10 and 80% by weight and even more preferably between 25 and 60% by weight of the composition.
  • Suitable excipients and/or carriers include maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethyl cellulose, corn starch, modified starch, fibersol, gelatine, hydroxypropylmethyl cellulose and the like (including mixtures thereof).
  • Preferable carriers include calcium carbonate, magnesium stearate, maltodextrin, dicalcium phosphate, modified starch, microcrystalline cellulose, fibersol, gelatine, hydroxypropylmethyl cellulose and mixtures thereof.
  • the various ingredients and the excipient and/or carrier may be mixed and formed into the desired form using common methods well known to the skilled person.
  • the administration form according to the present invention which is suited for the oral route, such as e.g. tablet or capsule, may be coated with a coating which is resistant against low pH values (approximately pH 1 to 2.5) and which dissolves at a pH value of approximately 3.0 to 8.0, preferably at a pH value of 3.0 to 6.5 and particularly preferable at a pH value of 4.0 to 6.0.
  • An optionally used coating should be in accordance with the pH optimum of the enzyme used and its stability at pH values to which the formulation will be exposed. Also a coating may be used which is not resistant to low pH values but which delays the release of the enzyme at low pH values.
  • the agent according to the present invention as coated (see above) pellets, granules or micro-/mini-tablets which can be filled into coated or non-coated capsules or which can be pressed into coated or non-coated tablets.
  • Suitable coatings are, for example, cellulose acetate phthalate, cellulose derivates, shellac, polyvinylpyrrolidone derivates, acrylic acid, polyacrylic acid derivates and polymethyl methacrylate (PMMA), such as e.g. Eudragit® (from Röhm GmbH, Darmstadt, Germany), in particular Eudragit® L30D-55.
  • the coating Eudragit® L30D-55 is dissolved, for example, at a pH value of 5.5 and higher.
  • this may be achieved e.g. by the addition of sodium hydroxide solution to the coating agent Eudragit® L30D-55, because in this case carboxyl groups of the methacrylate would be neutralised. Therefore, this coating will be dissolved, for example, already at a pH value of 4.0 provided that 5% of the carboxyl groups are neutralised.
  • the addition of about 100 g of 4% sodium hydroxide solution to 1 kg of Eudragit® L30D-55 would result in a neutralisation of about 6% of the carboxyl groups.
  • suitable acceptable carriers or adjuvants for use in the present invention include, but are not restricted to water, mineral oil, ethylene glycol, propylene glycol, lanolin, glyceryl stearate, sorbitan stearate, isopropyl myristate, isopropyl palmitate, acetone, glycerine, phosphatidylcholine, sodium cholate or ethanol.
  • compositions for use in the present invention may also comprise at least one co-emulsifying agent which includes but is not limited to oxyethylenated sorbitan monostearate, fatty alcohols, such as stearyl alcohol or cetyl alcohol, or esters of fatty acids and polyols, such as glyceryl stearate.
  • co-emulsifying agent includes but is not limited to oxyethylenated sorbitan monostearate, fatty alcohols, such as stearyl alcohol or cetyl alcohol, or esters of fatty acids and polyols, such as glyceryl stearate.
  • the agents according to the present invention may be provided in a stabilized form.
  • stabilization methods and procedures which may be used according to the present invention include any and all methods for the stabilization of chemical or biological material which are known in the art, comprising e.g. the addition of chemical agents, methods which are based on temperature modulation, methods which are based on irradiation or combinations thereof.
  • Chemical agents that may be used according to the present invention include, among others, preservatives, acids, bases, salts, antioxidants, viscosity enhancers, emulsifying agents, gelatinizers, and mixtures thereof.
  • enzyme production is performed in a technical fermentation way using suitable microorganisms (bacteria, moulds, fungi).
  • suitable microorganisms bacteria, moulds, fungi.
  • strains are recovered from natural ecosystems according to a special screening protocol, isolated as pure cultures as well as improved in their properties with respect to the enzyme spectrum and biosynthesis performance (volume/time yield). Enzyme production may also be carried out by methods developed in the future.
  • 5-D-fructose dehydrogenase is commercially available (e.g. Sigma-Aldrich or Toyobo Enzymes, Japan) and is usually prepared in a microbiological way with the help of the microorganism Gluconobacter industrius.
  • Glucose isomerase is also commercially available (e.g. Sigma-Aldrich or Novozymes A/S, Denmark) and usually prepared in a microbiological way with the help of the microorganism Streptomyces murinus.
  • the invention is not limited to the enzymes that are commercially available at the moment, but generally relates to enzymes that can catalyze the conversion of fructose—specifically or non-specifically—to 5-keto-D-fructose, and of glucose—specifically or non-specifically—to fructose.
  • a person skilled in the art can prepare suitable further enzymes by conventional methods, for example by mutagenesis of the gene encoding 5-D-fructose dehydrogenase which is present in Gluconobacter industrius or by mutagenesis of the gene encoding glucose isomerase in streptomyces murinus.
  • the enzymes may also be prepared with the help of other microorganisms, such as fungi, in sufficient amounts and the required purities, also by the use of the genetic engineering methods which are presently known or may be developed in the future. For example, if it is desired to produce the enzymes with other microorganisms, then the genetic information of a microorganism which has been found initially by extensive screening and which has been proven to be a suitable source of the enzyme with the desired properties can be transferred to a microorganism which is normally used for the production of enzymes. Also the modification of the enzyme(s) and the production of the enzyme(s) by means of methods which are presently known or may be developed in the future in the area of industrial enzyme development and enzyme production, such as genetic engineering, is possible.
  • the activity of 5-D-fructose dehydrogenase is defined in units (assay available e.g. from Sigma-Aldrich), whereby one unit is the amount of 5-D-fructose dehydrogenase that converts one micromole of D-fructose to 5-keto-D-fructose per minute at pH 4.5 and 37° C.
  • the activity of 5-D-fructose dehydrogenase per dose unit should be between 10 and 5 million units, preferably between 25 and 2.5 million units and particularly preferably between 50 and 1 million units.
  • the composition should contain glucose isomerase in an amount of 0.01 to 100,000 GIU, preferably of 0.05 to 10,000 GIU and particularly preferably of 0.1 to 1,000 GIU per dose unit.
  • One unit of this enzyme is defined as a glucose isomerase unit (GIU).
  • GIU glucose isomerase unit
  • One GIU converts 1 g of glucose into fructose at a pH value of 6.0 and at a temperature of 37° C. from a solution of initially 10% (percent by weight, i.e. 10 g of glucose +90 g of water) in 5 minutes.
  • the wide range of the above mentioned dosages may be explained by the fact that the agent according to the present invention can be applied for many uses, such as the different categories of adiposity and its accompanying and resulting diseases, or simply the effort of persons of normal weight to limit the intake of calories for preventing weight gain. Furthermore, the different dosages also result from the fact that strongly varying amounts of fructose and glucose are administered to the body, depending on the respective food.
  • the agent according to the present invention may comprise one or more additional enzymes, such as invertase (syn. beta-fructofuranosidase or beta-fructosidase), lactase (syn. beta-galactosidase), maltase (syn. alpha-glucosidase), alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, cyclomaltodextrin glucantransferase (CGTase).
  • invertase saccharin, lactase (syn. beta-galactosidase), maltase (syn. alpha-glucosidase), alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, cyclo
  • These enzymes have the property of releasing fructose and/or glucose from fructose and/or glucose containing substances and foodstuffs—alone or in combination with one or more of these enzymes—, whereby the enzymes pullulanase and isoamylase also increase the efficiency of glucoamylase and beta-amylase. All these enzymes are commercially available (e.g.
  • 5-D-fructose dehydrogenase in combination with invertase or 5-D-fructose dehydrogenase in combination with glucose isomerase and invertase, or 5-D-fructose dehydrogenase in combination with glucose isomerase and lactase and invertase, still further 5-D-fructose dehydrogenase in combination with glucose isomerase, Invertase, alpha amylase, beta amylase, glucoamylase, maltase, iso-amylase and pullulanase (combination of 9 enzymes), or 5-D-fructose dehydrogenase in combination with glucose isomerase, alpha amylase, beta amylase, glucoamylase, maltase, iso-amylase and pullulanase as well as invertase and lactase (combination of 10 enzymes).
  • said invertase can release glucose and fructose from e.g. sucrose and said lactase can release glucose from lactose.
  • Beta-amylase breaks down e.g. 1,4-alpha bonds in starch, starting at the non-reducing end of the polysaccharide chain with cleaving of maltose, and glucose is released by the action of maltase on maltose.
  • the endogenic release of fructose and/or glucose from fructose- and/or glucose-containing substances or foodstuffs, in particular from sucrose and starch may also be promoted and accelerated, so that the conversion of fructose into 5-keto-D-fructose which is catalyzed by 5-D-fructose dehydrogenase and/or the conversion of glucose to fructose, which is effected by glucose isomerase, may occur earlier. Therefore, the addition of one or more of these enzymes to the agent according to the present invention may have the benefit of reducing the required amount of 5-D-fructose dehydrogenase and glucose isomerase.
  • the activity of invertase is measured in Sumner units (SU, assay available e.g. from Bio-Cat Inc., Troy, Va., USA).
  • An SU is defined as the amount of the enzyme which converts 1 mg of sucrose into glucose and fructose under standard test conditions within 5 minutes at 20° C. and a pH value of 4.5.
  • the activity of the invertase per dose unit should be between 50 and 250,000 SU, preferably between 100 and 150,000 SU and particularly preferably between 150 and 100,000 SU per dose unit.
  • lactase The activity of lactase is given in Food Chemical Codex (FCC) units (assay is published in the Food Chemical Codex, fifth edition, and also available e.g. from Bio Cat Inc. Troy, Va. or Amano Enzymes, Japan or from Sigma Aldrich). If the agent according to the present invention also contains lactase, the activity of the lactase per dose unit should be between 50 and 200,000 FCC units, preferably between 100 and 100,000 FFC units and particularly preferably between 150 and 50,000 FCC units.
  • FCC Food Chemical Codex
  • the activity of maltase is defined in units, wherein one unit is the amount of maltase which will convert maltose to D-glucose at a rate of one milligram per minute at 37° C. and a pH of 4.0 in a 10% maltose solution by weight.
  • the activity per dose unit should be between 100 and 100,000 units, preferably between 200 and 50,000 units and particularly preferably between 500 and 20,000 units.
  • the optional enzymes are added to the agent according to the present invention, they—as is the case for the 5-D-fructose dehydrogenase and the glucose isomerase—should be used in sufficient amounts so that they can develop a sufficient enzyme activity for the intended purpose, e.g. sufficient invertase, so that an amount of sucrose usually ingested with a normal meal (e.g. 15 g) can be cleaved, and/or lactase, so that an amount of lactose usually ingested with a normal meal (e.g. 10 g) can be cleaved.
  • sufficient invertase so that an amount of sucrose usually ingested with a normal meal (e.g. 15 g) can be cleaved
  • lactase so that an amount of lactose usually ingested with a normal meal (e.g. 10 g) can be cleaved.
  • the enzymes used can be for example in solid form, e.g. as crystalline or amorphous granules or powders, as a paste or as a liquid, as well as in other forms.
  • the enzyme is a free enzyme.
  • the enzyme may e.g. be immobilized on substrate, which can be powderized if necessary before the enzyme is used in accordance with the invention.
  • the activity of 5-D-fructose dehydrogenase should be between 10 and 250,000 units, preferably between 25 and 150,000 units and particularly preferably between 50 and 100,000 units per gram fructose in the foodstuff.
  • the agent also contains glucose isomerase and the agent according to the present invention is added to a foodstuff before eating or during production, the activity of glucose isomerase should be between 0.01 and 20,000 units, preferably between 0.05 and 10,000 units and particularly preferably between 0.1 and 1000 units per gram glucose in the foodstuff.
  • the agent according to the present invention is added to a foodstuff before eating or during production and if the agent contains 5-D-fructose dehydrogenase and glucose isomerase, the activity of 5-D-fructose dehydrogenase should be between 10 and 250,000 units, preferably between 25 and 150,000 units and particularly preferably between 50 and 100,000 units per gram of fructose and glucose combined contained in the foodstuff.
  • an electron acceptor to the agent according to the present invention at e.g. a ratio (acceptor:substrate) of 1:1 to 1:1,000, preferably at a ratio of 1:2 to 1:200, particularly preferably at a ratio of 1:10 to 1:50.
  • suitable acceptors include NAD+, NADP+, FAD+, vitamins, such as vitamin C, vitamin E or vitamin A, ferricyanide, ketones, aldehydes, 2,6-dichlorophenolindophenol, phenazine methosulfate, nitroblue tetrazolium (including mixtures thereof), but are not limited thereto.
  • the physiologically present electrolytes should be sufficient for the function of the glucose isomerase.
  • electrolytes to the agent according to the present invention, e.g. in an amount of 0.0001% to 0.1% of the substrate (glucose).
  • electrolytes include, but are not limited to, MgSO4, Na 2 CO 3 , NaHCO 3 , NaOH, Na 2 SO 4 , MgCO 3 , H 2 SO 4 , NaS 2 O 3 , NaS 2 O 5 (including mixtures thereof).
  • metal ions in particular cations, such as Mn 2+ , Mg 2+ , Ca 2+ , Zn 2+ , Fe 2+ , Co 2+ or Cu 2+ , including mixtures thereof, to the agent according to the present invention, namely preferably in a molar ratio of 10 ⁇ 6 to 10 ⁇ 2 .
  • Mn 2 + is a suitable cation.
  • Capsule sizes mentioned below refer to the size definitions used by Capsugel Belgium BVBA, Bornem, Belgium.
  • the size of the capsules should be chosen according to the specific formulation of the agent.
  • a composition according to the present invention for the production of capsules may consist of 370 mg of 5-D-fructose dehydrogenase with an activity of 90 units/mg and 100 mg of dicalcium phosphate per capsule.
  • a dosage form according to the present invention consists of capsules (size 1) that contain 110 mg of 5-D-fructose dehydrogenase with an activity of 500 units/mg as well as 50 mg of invertase with an activity of 200 SU units/mg as well as 50 mg of maltase with an activity of 200 units/mg and 90 mg of maltodextrin.
  • Another example for the dosage form according to the present invention consists of capsules of size 00 which contain 200 mg of 5-D-fructose dehydrogenase with an activity of 500 units/mg as well as 100 mg of invertase with an activity of 200 SU units/mg as well as 150 mg of dicalcium phosphate.
  • a capsule of size 0 may contain 250 mg of 5-D-fructose dehydrogenase with an activity of 90 units/mg and 20 mg of glucose isomerase with an activity of 1 GIU/mg and 50 mg dicalcium phosphate.
  • a further example of a combination preparation with 5-D-fructose dehydrogenase and glucose isomerase for the production of capsules of size 00 may contain 370 mg of 5-D-fructose dehydrogenase with an activity of 90 units/mg, 30 mg of glucose isomerase with an activity of 1 GIU/mg and 70 mg of dicalcium phosphate.
  • a further example of a combination preparation with 5-D-fructose dehydrogenase and glucose isomerase for the production of capsules of size 00 may contain 110 mg of 5-D-fructose dehydrogenase with an activity of 500 units/g, 50 mg of glucose isomerase with an activity of 1 GIU/mg, 100 mg of invertase with an activity of 200 SU units/mg, 90 mg of lactase with an activity of 100 FCC units/mg and 120 mg of dicalcium phosphate.
  • a further example of a combination preparation with 5-D-fructose dehydrogenase and glucose isomerase for the production of capsules may consist of 55 mg of 5-D-fructose dehydrogenase with an activity of 1000 units/mg, 50 mg of glucose isomerase with an activity 1 GIU/mg and 55 mg of dicalcium phosphate per capsule.
  • a further example for a dosage form according to the present invention consists of capsules (size 00) that contain 165 mg of 5-D-Fructose dehydrogenase with an activity of 1000 units/mg, 150 mg of glucose isomerase with an activity of 1 GIU/mg and 155 mg of dicalcium phosphate per capsule.
  • the invention may for example contain between 10 and 5 million units of 5-D-fructose dehydrogenase per dose unit.
  • suitable additives in the required amount may be used.
  • the invention may be provided for medical purposes and non-medical purposes, e.g. as a pharmaceutical composition, medical device, foodstuff or special foodstuff.
  • the content of calories of carbohydrate containing food that can be utilized by the body can be reduced to such a degree that a marked weight loss can be achieved or a weight gain can be prevented despite the intake of carbohydrate rich food.
  • the agents according to the present invention are thus suitable for use in methods for the therapeutic treatment of the human or animal body in which a limitation or reduction of the intake of food calories originating from carbohydrates is intended, e.g. in the case of the therapy of diseases of the cardiovascular system (e.g. hypertension, coronary heart disease, venous insufficiency, heart failure, left-ventricular hypertrophy, arteriosclerosis), of metabolic and hormonal function (e.g.
  • diabetes mellitus type II dyslipidemias, hyperuricemia, hyperlipoproteinemia
  • the respiratory system e.g. sleep apnea, Pickwickian syndrome
  • the hepatobiliary system e.g. fatty liver, cholecystolithiasis
  • the locomotor system e.g. gonarthrosis, heel spur, arthrosis of the ankle joint
  • the skin e.g. intertrigo, hirsutism, striae
  • neoplasias e.g. increased risk of endometrial, breast, cervical, gall bladder cancer, etc.
  • disorders of sexual function e.g.
  • agents according to the present invention are in particular suitable for use in the case of adiposity and for the therapeutic treatment of adiposity.
  • fructose equivalent-containing refers to all substances and foodstuffs that contain fructose (a) as fructose per se, (b) in a form from which fructose can be released in the digestive tract (e.g. by cleavage as fructose from a saccharide chain containing at least two saccharide monomers), (c) in a form that can be converted to fructose, e.g. as glucose per se, or (d) in a form that can be released in the digestive tract and converted to fructose, e.g. as a saccharide chain containing at least two saccharide monomers, at least one of which can be cleaved from the saccharide chain as glucose.
  • total fructose refers to the total content of fructose in a foodstuff (a) as fructose per se, (b) in a form from which fructose can be released in the digestive tract (e.g. by cleavage as fructose from a saccharide chain containing at least two saccharide monomers), (c) in a form that can be converted to fructose, e.g. as glucose per se, or (d) in a form that can be released in the digestive tract and converted to fructose, e.g. a saccharide chain containing at least two saccharide monomers, at least one of which can be cleaved from the saccharide chain as glucose.
  • the term “effective fructose content” of an item refers to the effective amount of total fructose in that item, taking into account the prior action of fructose converting enzymes that have been added to the item or the future action of fructose converting enzymes that have been added to the item.
  • a foodstuff having a given fructose content and having microencapsulated 5-D-fructose dehydrogenase incorporated therein will have a lower effective fructose content than a foodstuff which lacks the microencapsulated 5-D-fructose dehydrogenase but is otherwise identical, since release of the 5-D-fructose dehydrogenase after ingestion will result in at least a portion of the fructose in the foodstuff being converted to 5-keto D-fructose.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Molecular Biology (AREA)
US12/094,648 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity) Abandoned US20090060956A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/094,648 US20090060956A1 (en) 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Applications Claiming Priority (18)

Application Number Priority Date Filing Date Title
DE102005056170.5 2005-11-23
DE102005056170 2005-11-23
DE102005060767 2005-12-16
DE102005060767.5 2005-12-16
DE102005061330.6 2005-12-20
DE102005061330 2005-12-20
DE102005063194.0 2005-12-30
DE102005063194 2005-12-30
DE102006001016 2006-01-05
DE102006001016.7 2006-01-05
US75741306P 2006-01-10 2006-01-10
DE102006013623A DE102006013623A1 (de) 2005-11-23 2006-03-22 Mittel zur Verminderung des verwertbaren Kaloriengehalts der Nahrung und zur therapeutischen Gewichtsabnahme. Insbesondere zur Anwendung bei Adipositas (Fettsucht)
DE102006013623.3 2006-03-22
DE102006014420A DE102006014420A1 (de) 2006-03-27 2006-03-27 Mittel zur Verminderung des verwertbaren Kaloriengehalts der Nahrung und zur therapeutischen Gewichtsabnahme, insbesondere zur Anwendung bei Adipositas (Fettsucht)
DE102006014420.1 2006-03-27
US83117306P 2006-07-17 2006-07-17
US12/094,648 US20090060956A1 (en) 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
PCT/EP2006/011231 WO2007059955A2 (en) 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/011231 A-371-Of-International WO2007059955A2 (en) 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14/946,772 Continuation US10624954B2 (en) 2005-11-23 2015-11-19 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Publications (1)

Publication Number Publication Date
US20090060956A1 true US20090060956A1 (en) 2009-03-05

Family

ID=37808214

Family Applications (3)

Application Number Title Priority Date Filing Date
US12/094,648 Abandoned US20090060956A1 (en) 2005-11-23 2006-11-23 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
US13/681,366 Abandoned US20130236593A1 (en) 2005-11-23 2012-11-19 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
US14/946,772 Active US10624954B2 (en) 2005-11-23 2015-11-19 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Family Applications After (2)

Application Number Title Priority Date Filing Date
US13/681,366 Abandoned US20130236593A1 (en) 2005-11-23 2012-11-19 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
US14/946,772 Active US10624954B2 (en) 2005-11-23 2015-11-19 Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)

Country Status (8)

Country Link
US (3) US20090060956A1 (ko)
EP (1) EP1951289B1 (ko)
JP (1) JP2009519900A (ko)
KR (1) KR20080084982A (ko)
AU (1) AU2006316815A1 (ko)
CA (1) CA2669247C (ko)
IL (1) IL191364B (ko)
WO (1) WO2007059955A2 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090311232A1 (en) * 2007-02-20 2009-12-17 Daniel Henry Wyrobnik Agent for use in the case of fructose intolerance

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI1951290T1 (en) * 2005-11-16 2018-04-30 Pro Natura Gesellschaft Fuer Gesunde Ernaehrung Mbh A device for use in the case of fructose intolerance
EP1987726A1 (en) * 2007-05-01 2008-11-05 Friesland Brands B.V. Good tasting food product containing a neutralisation agent for adverse compounds
CN101391101B (zh) * 2007-09-21 2011-06-08 光明乳业股份有限公司 环糊精葡基转移酶的新用途
US20170056485A1 (en) * 2015-08-31 2017-03-02 Sciotec Diagnostic Technologies Gmbh Crystallized xylose isomerase in prevention of the development of non-alcoholic fatty liver disease

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4107291A (en) * 1969-06-05 1978-08-15 Sankyo Company Limited Compositions for cleaning teeth and oral cavity
US4396602A (en) * 1981-09-22 1983-08-02 Asahi Kasei Kogyo Kabushiki Kaisha Blood glucose level lowering agents
US4699882A (en) * 1984-06-25 1987-10-13 Suomen Sokeri Oi Stable glucose isomerase concentrate and a process for the preparation thereof
US6165500A (en) * 1990-08-24 2000-12-26 Idea Ag Preparation for the application of agents in mini-droplets
US6306445B1 (en) * 1998-05-13 2001-10-23 Novozymes Biotech Inc. Methods for using dehydrogenases in baking
US6395299B1 (en) * 1999-02-12 2002-05-28 Biostream, Inc. Matrices for drug delivery and methods for making and using the same
US20020187536A1 (en) * 1995-06-29 2002-12-12 Kulkarni Sunanda R. Stable lactase tablets and methods of production
US20030049337A1 (en) * 2001-09-11 2003-03-13 Nagaoka Perfumery Co., Ltd Composition for preventing fructose absorption
US20030113310A1 (en) * 2001-12-17 2003-06-19 Van Laere Katrien Maria Jozefa Method for the treatment of obesity, overweight and fluctuations in blood insuline and/or glucose levels
US6663903B1 (en) * 1998-05-29 2003-12-16 Novozymes A/S Methods for using xyloglucan endotransglycosylase in baking
US20080044504A1 (en) * 2004-07-05 2008-02-21 Marukin Bio, Inc. Pomegranate Juice, Pomegranate Juice Powder and Process for Producing the Powder

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI905402A (fi) * 1990-11-01 1992-05-02 Alko Ab Oy Oligosackaridblandning och foerfarande foer dess efterbehandling.
EP1011700B1 (en) * 1997-06-17 2002-09-04 Novozymes A/S An oral care composition comprising a bacillus pullulanase and a dextranase
JPH11255802A (ja) * 1998-03-10 1999-09-21 Nippon Starch Chem Co Ltd 難消化性澱粉及びその製造方法
US6042823A (en) * 1998-07-02 2000-03-28 Amano Pharmaceuticals Co., Ltd. Enzyme composition and use thereof
SI1951290T1 (en) * 2005-11-16 2018-04-30 Pro Natura Gesellschaft Fuer Gesunde Ernaehrung Mbh A device for use in the case of fructose intolerance
EP1951293B1 (en) * 2005-11-23 2015-09-09 Pro Natura Gesellschaft für Gesunde Ernährung mbH Agent for use in the case of disorders of blood sugar metabolism, including diabetes
DE102007008664B4 (de) * 2007-02-20 2021-07-29 Vitacare Gmbh & Co. Kg Mittel zur Anwendung bei Fructoseintoleranz

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4107291A (en) * 1969-06-05 1978-08-15 Sankyo Company Limited Compositions for cleaning teeth and oral cavity
US4396602A (en) * 1981-09-22 1983-08-02 Asahi Kasei Kogyo Kabushiki Kaisha Blood glucose level lowering agents
US4699882A (en) * 1984-06-25 1987-10-13 Suomen Sokeri Oi Stable glucose isomerase concentrate and a process for the preparation thereof
US6165500A (en) * 1990-08-24 2000-12-26 Idea Ag Preparation for the application of agents in mini-droplets
US20020187536A1 (en) * 1995-06-29 2002-12-12 Kulkarni Sunanda R. Stable lactase tablets and methods of production
US6306445B1 (en) * 1998-05-13 2001-10-23 Novozymes Biotech Inc. Methods for using dehydrogenases in baking
US6663903B1 (en) * 1998-05-29 2003-12-16 Novozymes A/S Methods for using xyloglucan endotransglycosylase in baking
US6395299B1 (en) * 1999-02-12 2002-05-28 Biostream, Inc. Matrices for drug delivery and methods for making and using the same
US20030049337A1 (en) * 2001-09-11 2003-03-13 Nagaoka Perfumery Co., Ltd Composition for preventing fructose absorption
US20030113310A1 (en) * 2001-12-17 2003-06-19 Van Laere Katrien Maria Jozefa Method for the treatment of obesity, overweight and fluctuations in blood insuline and/or glucose levels
US20080044504A1 (en) * 2004-07-05 2008-02-21 Marukin Bio, Inc. Pomegranate Juice, Pomegranate Juice Powder and Process for Producing the Powder

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090311232A1 (en) * 2007-02-20 2009-12-17 Daniel Henry Wyrobnik Agent for use in the case of fructose intolerance
US8460911B2 (en) 2007-02-20 2013-06-11 Vitacare Gmbh & Co. Kg Agent for use in the case of fructose intolerance

Also Published As

Publication number Publication date
US10624954B2 (en) 2020-04-21
IL191364B (en) 2020-06-30
US20130236593A1 (en) 2013-09-12
JP2009519900A (ja) 2009-05-21
CA2669247A1 (en) 2008-05-31
WO2007059955A2 (en) 2007-05-31
EP1951289A2 (en) 2008-08-06
WO2007059955A3 (en) 2007-09-27
US20160175404A1 (en) 2016-06-23
EP1951289B1 (en) 2018-11-14
CA2669247C (en) 2016-05-17
AU2006316815A1 (en) 2007-05-31
KR20080084982A (ko) 2008-09-22

Similar Documents

Publication Publication Date Title
US10568942B2 (en) Agent for use in the case of fructose intolerance
US10624954B2 (en) Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
US9415093B2 (en) Agent for use in the case of disorders of blood sugar metabolism, including diabetes
CA2890721C (en) Agent for use in the case of fructose intolerance
AU2013211517B2 (en) Agent for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in the case of adiposity (obesity)
US20090214620A1 (en) Agent for use in the case of disorders of blood sugar metabolism, including diabetes
NZ569118A (en) Agent comprising 5-D-fructose dehydrogenase in combination with one or more other enzymes for reducing the useable calorie content of food and for therapeutic reduction of weight, in particular for use in case of adiposity (obesity)
NZ569117A (en) Agent comprising 5-D-fructose dehydrogenase for use in the case of fructose intolerance

Legal Events

Date Code Title Description
AS Assignment

Owner name: PRO NATURA GESELLSCHAFT FUR GESUNDE ERNAHRUNG MBH,

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WYROBNIK, DANIEL HENRY;WYROBNIK, ISAAC HARRY;SILCOFF, ELLIAD RONEN;REEL/FRAME:022334/0491;SIGNING DATES FROM 20081026 TO 20081107

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION