DE102006014420A1 - New 5-D-fructose dehydrogenase in combination with an enzyme, e.g. glucose isomerase, useful for preventing or treating adiposity - Google Patents

Abstract

A 5-D-fructose dehydrogenase, optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase (CGTase), for use in medicine, is new. Independent claims are: (1) a pharmaceutical composition comprising 5-D-fructose dehydrogenase optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase; (2) a medical device comprising 5-D-fructose dehydrogenase optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase; (3) a foodstuff comprising 5-D-fructose dehydrogenase in combination with invertase and/or maltase and/or lactase; (4) a special foodstuff comprising 5-D-fructose dehydrogenase optionally in combination with one or more enzymes selected from glucose isomerase, invertase, lactase, maltase, alpha-amylase, beta-amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase; (5) a process for the treatment of a foodstuff; (6) a mammalian-ingestible composition, which comprises an enzyme that converts D-fructose into a form that is biologically inactive in a selected mammalian body or a mixture of such enzymes; (7) a mammalian-ingestible composition, which comprises an enzyme that converts D-fructose into a form that cannot be digested in a selected mammalian digestive tract; (8) a mammalian-ingestible composition, which comprises an enzyme that converts D-fructose into a form that is not metabolizable in a selected mammalian body; (9) a method of treating adiposity in a mammalian subject body; (10) a method of reducing the effect of D-fructose on a mammalian subject body; (11) a method of reducing the effect of total fructose on a mammalian subject body; (12) a kit comprising an enzyme that converts D-fructose into a form that is at least one of (a) biologically inactive in a selected mammalian body, (b) not digestible in the digestive tract of the mammalian body, and (c) not metabolizable in the mammalian body, or a mixture of such enzymes, and instructions explaining how to use the enzyme or mixture to reduce the effects of fructose in the mammalian body; (13) a reduced-total fructose foodstuff; (14) a method for preparing a reduced-total fructose foodstuff; and (15) a method for preparing a foodstuff or foodstuff precursor having a reduced effective fructose content. ACTIVITY : Anorectic. No biological data given. MECHANISM OF ACTION : None given.

Description

object The invention is a means for reducing the usable calorie content the food that contains a compound that causes the dehydration of Fructose causes 5-keto-D-fructose. The 5-keto-D-fructose may be present in the human or animal organism can not be recycled and is therefore not available to him as a calorie source. object The invention is also an agent which additionally a Contains compound converts the glucose into fructose.

Fructose is known to be a ketohexose and is an important energy-supplying food ingredient. It is present as a di- and oligosaccharide, but also as a free fructose in numerous foods. Unlike glucose, fructose is absorbed into the mucosal cells of the small intestine by facilitated carrier-mediated diffusion. Enzymatic degradation begins in the liver by the action of adenosine triphosphate (ATP) -dependent fructokinase, whereby fructose is converted to fructose-1-phosphate. In the liver and kidneys, fructose-1-phosphate is cleaved by aldolase B into glyceraldehyde and dihydroxyacetone phosphate according to the reaction scheme shown below:

fructose is in the diet in z. B. fruits and fruit juices in big Amount contained, but especially in sucrose, which in the organism is split into fructose and glucose. Fructose is thus an important one Calorie supplier of the human organism and must at all efforts To reduce the calorie content of the food, special attention Find. Under fructosehaltig in the following all substances and Foods are understood which either fructose in pure form contain or from which released fructose in the digestive tract can be.

deviations from the standard weight due to the increase in body mass, predominantly fat, are called obesity, wherein, as a rule and in the sense of this invention, four stages are distinguished be, namely Grade 0 = normal weight, grade I = overweight, grade II = obesity and grade III = extreme obesity. The classification in the individual Stages are over the known body mass index (BMI). With increase of the fatty tissue and thus of body weight over one certain thresholds, various diseases increasingly occur such as Hypertension, and life expectancy is decreasing. The number obese (Grade I to grade III obesity) has over the last few decades in the industrialized countries constantly increased and amounts currently depending on the statistics and definition of the term overweight or Obesity 30-50 % of the total population. In the Federal Republic of Germany z. For example, every second citizen is overweight (Grade I obesity) and every sixth obese (obesity grade II or III).

at Children are rising as a result of malnutrition and lack of exercise Share of adipose alike. The therapy is limited so far on nutritional therapy and in extreme cases on surgical procedures. As is known, there is a very high and steadily growing number of nutritional therapies and diets, which usually do not lead to sustainable success. It comes, even if initially sets a weight loss, mostly to the so-called yo-yo effect, i.e. that those affected first decrease, but after completion or premature termination the diet increase again. Not infrequently, the body weight is finally even higher than before the start of the diet. The only in very serious cases The surgical measures to be used are aimed at the Nutrient supply or the nutrient utilization to reduce and are with high operational risks and long-term associated with negative side effects. Thus, as a result of resorption impairments and inadequate nutritional intake to stop nutrient deficiencies. These concern vitamins, minerals, and protein. At to one third of those who are operated have a folic acid deficiency one. Furthermore It can lead to iron, potassium, magnesium and vitamin A deficiency states.

The previously known drug therapies are discussed controversially. Previously, products had to be repeatedly withdrawn from the market because of serious side effects. All currently available drugs also have significant, unpleasant and common side effects, such. As fatty stools, constipation and insomnia. One to lead to a regular and sustainable success en Diet and / or a widely used and side-effect-free therapy of obesity in its various forms is not known. The widespread use of surgical procedures is of course out of the question. It remains to be stated that the persons concerned and the treating professionals are in a rather hopeless and frustrating situation on the whole.

One Means, which are not on the organism, but on the carbohydrates in the diet and the usable calorie content of the Would reduce food, would be one very widespread and urgent for decades desire to satisfy. Such a remedy would also overcome one in the professional world and in the affected persons established prejudice, namely, that a lasting weight reduction or the prevention of a Weight gain without suffering and without a significant change the nutritional habits not possible be, mean and a very significant improvement and leaps and bounds Further development of therapy and nutritional options in obesity. Also would such a means the end of the hitherto unsuccessful efforts of Mean a wide, easy and long-term applicable and to find side effect-free agent for use in obesity. All of this would all the more for to apply a remedy which as well would have no negative health side effects.

Consequently It is an object of the present invention to provide a means to Make the usable calorie content of the food significantly reduced, in particular to the intake usually fructosehaltiger Foods also allow for obesity without this lead to an increase in weight would. Furthermore, it is an object of the invention Obese foods accessible to which you have consumed so far because of their fructose content were denied or their consumption for those with negative health consequences. Furthermore, a means be provided, which after ingestion of fructose at Obesity associated negative health consequences, in particular increase, reduce or prevent weight gain.

object The invention is therefore an agent which is all described above solve problems can. The agent contains 5-D-fructose dehydrogenase (syn. fructose 5-dehydrogenase). The agent according to the invention can cause the fructose in the diet by dehydration is converted to 5-keto-D-fructose. This will change it so that they in the metabolism of the human or animal organism is no longer used. A 5-D-fructose dehydrogenase in the sense This invention is an enzyme that causes dehydration of fructose to catalyze 5-keto-D-fructose. A possible production process for 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 practical meaning of such a means for the reduction of salable calorie content of the food also becomes clear when one considers, that fructose in very large Scope is used in the food industry as a sweetener. at Foods that contain sucrose may have the calorie content by the use of the agent according to the invention which contains the enzyme Contains 5-D-fructose dehydrogenase, approximately be halved. While digestion, the sucrose is enzymatically converted into glucose and fructose split. The fructose content (50% of that contained in sucrose Calories) is converted to 5-keto-D-fructose by 5-D-fructose dehydrogenase dehydrated and can then no longer be utilized by the organism.

glucose is the central carbohydrate of energy and substrate metabolism. It is the basic building block of many polysaccharides (eg starch).

A Further reduction of the calorie content of the diet can therefore according to the invention a means can be achieved which, as an additional active ingredient glucose isomerase (syn. glucose-6-phosphate isomerase). A glucose isomerase in the The meaning of this invention is an enzyme capable of producing glucose into fructose.

One Such combining agent may also be in the form of two separate Dose units, z. B. in two separate tablets, are used, one containing glucose isomerase and the other 5-D-fructose dehydrogenase.

By combining the 5-D-fructose dehydrogenase with the enzyme glucose isomerase, both ingested glucose and glucose released by the breakdown of carbohydrates is largely removed from the body's calorie metabolism. The glucose isomerase be has the property of converting glucose into fructose and vice versa. Depending on the temperature present, equilibrium is established with about 48 to 49% glucose and 51 to 52% fructose. Such an enzyme combination consisting of 5-D-fructose dehydrogenase and glucose isomerase is ideally suited to the calorie content of z. B. starchy food, such as potatoes to reduce significantly. Since glucose is released as a monosaccharide from starch during digestion, it is converted by glucose isomerase into fructose, which is then converted by 5-D-fructose dehydrogenase into 5-keto-D-fructose which is not usable by the body. The 5-D-fructose dehydrogenase prevents so that the above-described balance can be established. Therefore, the glucose isomerase will convert glucose to fructose, which in turn is dehydrated by 5-D-fructose dehydrogenase to 5-keto-D-fructose, until there is no more glucose in the diet or chyme.

Also with sucrose can be achieve greater calorie reduction with the combination agent. The while the digestion of the fructose released from the sucrose is how described above, from the 5-D-fructose dehydrogenase converted into 5-keto-D-fructose. The glucose isomerase will then try compensate for the resulting imbalance in which they glucose converted to fructose. This conversion process will turn that way continue for a long time until there is no more glucose in the chyme is. In this way, the for the organism available Calorie content of sucrose-containing foods are more reduced than when using 5-D-fructose dehydrogenase alone.

By the inventive combination agent So it's going to be a big one Part of the organism fed or glucose released in the digestive tract is converted to fructose and then in a second reaction step in the for the calorie metabolism worthless 5-keto-D-fructose converted.

object The invention is also an agent which, with the aid of a 5-D-fructose dehydrogenase - alone or in combination with a glucose isomerase - the bioavailability reduced by fructose in the human or animal organism.

object The invention further provides a means for reducing the recoverable Calorie content of the diet containing a 5-D-fructose dehydrogenase - alone or in combination with a glucose isomerase.

object the invention is further an agent for use in obesity, a 5-D-fructose dehydrogenase - alone or in combination with a glucose isomerase - contains.

object The invention is also an agent containing a 5-D-fructose dehydrogenase - alone or in combination with a glucose isomerase - for use with obesity associated health problems and diseases, including diseases of the cardiovascular Systems (eg hypertension, coronary heart disease, venous insufficiency, Heart failure, left ventricular Hypertrophy), metabolic and hormonal function (eg Type II diabetes mellitus, dyslipidemias, hyperuricemia, hyperlipoproteinemia), of respiratory system (eg sleep apnea, Pickwick's syndrome), of the hepatobilliary System (eg fatty liver, cholecystolithiasis), the musculoskeletal system (eg gonarthrosis, heel spurs, ankle osteoarthritis), the skin (eg, Intertrigo, Hirsutimus, Striae) and for use with Adiposity associated with neoplasia (eg increased risk of endometrial, Mammary, cervical-gallbladder carcinoma, etc.), disorders of sexual function (e.g. B. reduced fertility, Complications at birth), psychosocial problems (eg diminished self-confidence, social isolation, discrimination, partner and professional problems) and other problems, such. B. a reduced mobility and perseverance, increased Operation risk and difficult examination conditions.

All These diseases and health problems are common Associated with obesity.

One Another object of the invention is the use of a 5-D-fructose dehydrogenase - alone or in combination with a glucose isomerase - in obesity and with Obesity-related health problems and diseases (see above).

According to the invention, a 5-D-fructose dehydrogenase alone or in combination with glucose isomerase also to reduce the usable calorie content in a food be used. To the food in the sense of this invention counting including dietary ones Food, nutritional supplements, balanced diets and food additives.

The invention makes it possible in a particularly simple way fructose in a food in a mold to convict, which avoids weight gain or allows for weight loss. Thus, the invention also makes it possible to make such food available for consumption by the adipose, which previously had to be avoided by those affected because of their fructose and glucose content.

According to the invention is further 5-D-fructose dehydrogenase alone or in combination with glucose isomerase for use in medicine, for example as a medicament, specified. The invention accordingly is also a Product made from 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase or these - alone or in combination with glucose isomerase - in addition to one or more contains other active substances, for use in a medical procedure, in particular a Method for the therapeutic treatment of human or animal Body. For the purposes of this invention, a drug is a product, in particular a substance or mixture of substances, for use in a process for surgical or therapeutic treatment of the human or animal body and diagnostic methods that are human or animal body be made. To the medicaments in the sense of the invention counting so that products, in particular substances or mixtures of substances, which are intended or suitable to cure, alleviate, obesity, to prevent or to recognize.

According to one In another aspect, according to the invention, a foodstuff is provided, 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase. Furthermore, according to the invention a food provided that 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase - in and also effective for converting fructose to 5-keto-D-fructose possibly glucose isomerase in one to convert glucose to fructose contains effective amount. Such a food can be advantageously obtained by a method for Treat a food produced where the food with a 5-D-fructose dehydrogenase - or with a 5-D-fructose dehydrogenase in combination with glucose isomerase - under such conditions is contacted, under which the 5-D-fructose dehydrogenase fructose to dehydrogenate 5-keto-D-fructose and glucose isomerase the Glucose can convert to fructose. Such a food possesses one opposite otherwise untreated foods reduced fructose content or a reduced content of fructose and glucose and is suitable Therefore, for the first time for consumption in obesity. Especially advantageous A food can be prepared by a process of the food with a 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase - is added in a manner in which the effect of the enzyme or the two enzymes only after eating the food. Such a 5-D-fructose deyhdrogenase or 5-D-fructose deoxygenase and glucose isomerase containing food has the same taste as an untreated food and is reduced due to the onset of consumption Fructose or fructose and glucose content for consumption for the first time suitable for obesity.

According to one Another aspect is according to the invention 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase - ready as a medical device posed. The invention accordingly is also a Medical device made from 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase - or these - alone or in combination with glucose isomerase - in addition to one or more contains other active ingredients.

The Invention will be further discussed in its various aspects described. As far as is spoken below of a means, is always a food, medical device or drug meant.

The 5-D-fructose dehydrogenase has been known for almost 40 years Compound, however, so far only for analytical purposes application has found. Glucose isomerase has been around for over 40 years known compound, previously only in the starch saccharification is used. Industrially, it will be both in immobilized form for converting glucose into fructose as well as for conversion used by fructose in glucose.

The 5-D-fructose dehydrogenase has not been previously and in particular not in combination with glucose isomerase in medicinal-pharmaceutical Range, especially for obesity in humans or animals. Consequently, the invention presented here is the first medical indication for 5-D-fructose dehydrogenase and the first medical indication for the combination of both Enzymes. Both enzymes have not been used for therapeutic treatment of the human or animal body or for diagnostic Purposes used on the human or animal body.

The agents according to the invention can orally before meals, at meal times or immediately thereafter be taken in order to dehydrate them in the porridge or unfolding effect on the fructose. Preferably are the agents of the invention immediately before meals while taken with meals or immediately after meals. The agents according to the invention can contain the enzyme without further additives. However, it is preferable that the inventive compositions furthermore pharmaceutically acceptable and / or food safe additives, such as Extenders, binders, stabilizers, preservatives, Flavoring agents, etc. Such additives are for the preparation of medicines, Medical devices, food, dietetic foods, nutritional supplements, balanced diets and food additives usual and well known and those skilled in the art know which additives are in which Quantities for certain dosage forms are suitable. Especially preferred contain the agents of the invention as additives di-calcium phosphate, lactose, modified starch, microcrystalline Cellulose, maltodextrin and / or Fibersol.

The agents according to the invention can be added to a food before consumption. You can do that Food even added in the production with the goal be effective only after eating the food unfold. this could optionally z. B. be achieved by a microencapsulation. This would the useful fructose content of the food on particularly advantageous Way without disadvantages for its taste is reduced. Therefore, preparations are preferred containing 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase -, the enzyme or these enzymes only in the digestive tract of a Human or animal release or otherwise effective leave, especially in the stomach or small intestine. The invention could therefore for example, in the production of desserts, fruit preparations (eg applesauce), jam, honey, chocolate and chocolate products, Baked goods (eg biscuits and cakes), bread products, pasta, vegetable dishes, Potato dishes, ice cream, cereals, dairy foods (eg fruit yoghurt and pudding), fructose-containing beverages, fructose-containing sauces (eg, tomato ketchup) and fructose-containing sweeteners. For food that is cooked or baked, the compositions of the invention after cooling z. B. mixed or sprinkled.

There in specially for Diabetic foods produced fructose on a large scale as sweetener is used is the addition of the compositions of the invention to diabetic food before consumption or the addition of the agents according to the invention particularly advantageous in the production of diabetic food, around obese Diabetics the consumption of diabetic food, such as. B. the above mentioned in their respective execution as diabetic nutrition, to enable.

The agents according to the invention can can also be added to a food to get its effect after the Consumed from fructose derived from another food and in the case of the combination agent also at the one from another Develop food-derived glucose. An example of this would be the addition the agents according to the invention to a spread, so that the reduction contained in the bread usable calories after eating the bread occurs without to affect the taste of the bread. Another example would be spice blends and mayonnaise among others for the use with French fries.

The 5-D-fructose dehydrogenase and the combination agent can also be used in immobilized form. This is special appropriate for Treat liquid Food. For example, 5-D-fructose dehydrogenase in a fructose-permeable one Be embedded in the matrix. If a fructose-containing liquid food is flowed along the enzyme-containing matrix, then the food deprived of fructose under the action of the enzyme and to 5-keto-D-fructose implemented

Inventive subject matter are also agents that in addition to other active ingredients in addition 5-D-fructose dehydrogenase, either alone or in combination with glucose isomerase.

The invention may be formulated in any form suitable for the intended route of administration. For oral administration, the compositions of the invention are preferably in the form of capsules (coated or uncoated), tablets (coated or uncoated), capsules containing coated or uncoated pellets, granules or micro or minitablets, tablets comprising coated or uncoated pellets, dragées or micro- or minitablets are pressed, gel caps or formulated in liquid form as a solution, drop, suspension or gel. The invention may also be present as a dried oral supplement or wet oral supplement. The formulation of the compositions according to the invention as a powder is particularly suitable for admixing with a foodstuff. The powder can be added to a meal or it can be mixed with a porridge or a drink. It is particularly expedient if the agent offered as loose powder is packaged in individual dosage amounts, such as in individual bags or capsules, or if it is provided in a dosing dispenser. Most preferably, the compositions according to the invention are formulated as powders or granules in capsules or as tablets which are administered orally.

to Oral administration may include the active ingredient 5-D-fructose dehydrogenase alone or in combination with glucose isomerase in compatible Excipients and / or carriers be included. The term "more compatible Carrier "refers to a carrier, for pharmaceutical use, which contains the active ingredient for its The site of action supplies and the recipient human or animal no cause considerable damage becomes. The concrete shape of the vehicle is not crucial.

The Total amount of vehicle and / or excipients for a 5-D-fructose dehydrogenase or 5-D-fructose dehydrogenase and glucose isomerase containing Means preferably between 5 and 99.9% by weight, more preferably between 10 and 95% by weight and even more preferably between 25 and 90% by weight of the composition.

suitable Excipients and / or carriers shut down Maltodextrin, calcium carbonate, di-calcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, Stearic acid, croscarmellose sodium, sodium, Crospovidone, sucrose, vegetable gums, lactose, methylcellulose, Povidone, carboxymethyl cellulose, corn starch, modified starch, fibrosol, Gelatin, hydroxypropyl methylcellulose and the like (including mixtures of it). Preferred carriers close calcium carbonate, Magnesium stearate, maltodextrin, di-calcium phosphate, modified Strength, microcrystalline cellulose, fibersol, gelatin, hydroxypropylmethycellulose and mixtures thereof. The different components and the Excipient and / or carrier are mixed and converted into the desired shape using conventional methods shaped. The inventive for oral Administration certain dosage form, such. B. tablet or Capsule, can be coated with a low-pH resistant coating be. It can also be a coating which is not resistant to low pH values, However, the release of the respective enzyme at low pH values delayed. It is also possible the agent of the invention as coated (see above) to produce pellets, granules or micro- or minitablets, which in uncoated Filled capsules or in uncoated Pressed tablets can be. Suitable coatings are for example, cellulose acetate phthalate, cellulose derivatives, shellac, Polyvinylpyrrolidone derivatives, acrylic acid, polyacrylic acid derivatives and polymethyl methacrylates (PMMA), such as. B. Eudragit (the Röhm GmbH, Darmstadt), in particular Eudragit FS30D and Eudragit L30D-55. By the addition of z. B. caustic soda to the coating agent Eudragit, can the pH resistance of this coating agent additionally affected become. More details about Methods of formulation and administration may be found in the 21st edition of Remington: The Science & Practice of Pharmacy, published in 2005 by Lippincott, Williams & Wilkins, Baltimore, USA and in Prof. Bauer "Textbook of Pharmaceutical Technology", 18th edition published in 2006 in the publishing house scientific publishing company (ISBN 3804-72222-9) are found, the documents hereby incorporated by reference become.

Other suitable pharmaceutically acceptable carrier or adjuvants for use in the present invention include but are not limited on, water, mineral oil, Ethylene glycol, propylene glycol, lanolin, glyceryl stearate, sorbitan stearate, Isopropyl myristate, isopropyl palmitate, acetone, glycerine, phosphatidylcholine, Sodium cholate or ethanol.

The Compositions for use in the present invention may also be at least a co-emulsifier 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.

Preferably become the agents to be used in the present invention provided in a stabilized form. In general shut down Stabilization methods and methods according to the present invention can be used any and all methods of stabilization known in the art of chemical or biological material, e.g. B. the Addition of chemical agents, methods based on temperature modulation; Methods based on radiation or combinations thereof. Dry Means, according to the present Invention can be used shut down including preservatives; Acids, bases; salts; antioxidants; viscosity; emulsifiers; gelling agent; and mixtures thereof.

The Industrial production of enzymes is conventionally carried out by fermentation technology using suitable microorganisms (bacteria, molds, Yeasts). The tribes be following a special screening program from natural ecosystems taken as pure cultures isolated and in their properties in terms of enzyme spectrum and biosynthetic performance (space / time yield) improved.

The 5-D-fructose dehydrogenase is commercially available (eg Sigma-Aldrich) and becomes common with the help of the microorganism Gluconobacter industrius microbiological produced. The glucose isomerase is also commercially available (e.g. B. Novozymes A / S, Denmark) and becomes common with the help of the microorganism Streptomyces murinus microbiological produced. However, the invention is not currently commercial available Limited enzymes, but generally relates to enzymes that are the implementation of fructose - specific or nonspecific - too 5-keto-D-fructose or to effect glucose. Suitable further enzymes can the expert with usual Produce process, for example by mutagenesis of Gluconobacter industrius existing gene for 5-D-fructose dehydrogenase or by mutagenesis in Streptomyces murinus present gene for Glucose isomerase. The enzymes can also be solved with the help of others Microorganisms, such. As mushrooms, in sufficient quantities and the required purities, even using the usual today genetic engineering process. Should it be z. B. be desired to produce the enzymes with other microorganisms, so could the genetic information first by an extensive one Screening microorganism, which is also known as suitable source for the enzyme with the desired Properties has been found to be one of the commonly used for enzyme production transferred used microorganism become. Also the change the enzyme (s) themselves and production of the enzyme (s) under Application of today in industrial Enzymentwicklung and enzyme production usual Methods, such. As genetic engineering is possible. The use and the Type of implementation all of these procedures for the development and production of the enzymes in the desired Purities and activities and with the desired Properties are well known to those skilled in the art. The versions in chapter 2 (page 82-page 130) of the textbook "Lebensmittel-Biotechnologie und Nutrition "by Heinz Ruttloff, Jürgen Proll and Andreas Leuchtenberger, published by Springer Verlag 1997 (ISBN 3-540-61135-5) describe these methods in detail and are hereby incorporated by reference into the patent application.

The activity 5-D-fructose dehydrogenase is defined in units where one unit is that amount of 5-D-fructose dehydrogenase that one micromole of D-fructose per minute at pH 4.5 and 37 ° C in 5-keto-D-fructose transforms. In general, the activity of 5-D-fructose dehydrogenase should be per unit dose between 10 and 5 million units, preferably between 25 and 2.5 million units, and most preferably between 50 and 1 million units.

at the combination agent according to the invention, which also contains glucose isomerase, should the composition Glucose isomerase in an amount or activity of 0.01 to 100,000 GIU, preferably 0.05 to 10,000 GIU and more preferably 0.1 to 1,000 GIU per dose unit. One unit of this enzyme is defined as glucose isomerase unit (GIU), which at a pH of 7.5 and a temperature of 37 ° C from an initial 10% solution (Percent by weight, i.e., 10 g fructose + 90 g water) in 5 minutes 1 g of fructose is converted to glucose.

The size Bandwidth of the above doses is explained in that the agent according to the invention many different applications has, such. For example, the different categories of obesity and their Accompanying and secondary diseases or even the aspiration of normal weight, limit the calorie intake to prevent weight gain. Furthermore The different dosages also result from the fact that depending on the organism varying amounts of fructose from each food and glucose supplied become.

Especially it is advantageous if the agent according to the invention also still contains one or more of the following enzymes: invertase (syn, beta-fructofuranosidase or beta-fructosidase), lactase (syn. beta-galactosidase), maltase (syn. alpha-glucosidase), Alpha-amylase, beta-amylase, Glucoamylase, pullulanase, isoamylase, cyclomaltodextrin glucan transferase (CGTase). These enzymes have the property alone or in Combination with other enzymes, fructose and / or glucose from substances containing glucose and foods, the enzymes being pullulanase and isoamylase also affects the effectiveness of glucoamylase and beta-amylase increase.

For example, the invertase can be glucose and fructose from e.g. For example, sucrose and the lactase release glucose from lactose. Beta-amylase decomposes z. For example, non-reducing 1,4-alpha bonds in starch the end of the polysaccharide chain with elimination of maltose and by the action of maltase on maltose glucose is released. By adding one or more of these enzymes to the composition according to the invention, therefore, the body's own release of fructose and / or glucose from fructose- and / or glucose-containing substances or foods, in particular from sucrose and starch, can be promoted and accelerated, so that the results obtained by the 5 D-fructose dehydrogenase catalyzed conversion of fructose to 5-keto-D-fructose and / or the glucose isomerase-induced conversion of glucose to fructose can take place more rapidly. Therefore, by the addition of one or more of these enzymes to the agent of the invention would also advantageously a reduction of the required amount of 5-D-fructose dehydrogenase and glucose isomerase possible. All of these enzymes are commercially available (eg, BioCat Inc., Troy, USA or Novozymes, A / S, Denmark or Amano Enzymes Inc., Japan) and have so far been used in combination with 5-D-fructose dehydrogenase - alone or in combination with glucose isomerase - never used in the medical-pharmaceutical field, especially not in obesity.

The activity of invertase is given in Sumner units (SU). An SU is defined as the amount of enzyme required to 1 mg of sucrose in 5 minutes under standard test conditions at 20 ° C and a pH of 4.5 into glucose and fructose. should that inventive agent also contain invertase, so should the activity of invertase per unit dose between 50 and 200,000 SU, preferably between 100 and 100,000 SU and more preferably between 150 and 50,000 SU per dose unit lie.

The activity Lactase is reported in Food Chemical Codex (FCC) units. Should the inventive agent also contain lactase, so should the activity of the lactase per unit dose between 50 and 200,000 FCC units, preferably between 100 and 100,000 FCC units and especially preferably between 150 and 50,000 FCC units per dose unit lie.

If the agent of the invention added to a food before consumption or during production will, so should the activity 5-D-fructose dehydrogenase between 10 and 100,000 units, preferably between 25 and 60,000 Units, and more preferably between 50 and 25,000 units per gram of fructose are in the food. If both enzymes are used and the agent according to the invention a food should be added before consumption or during production the activity the glucose isomerase between 0.01 and 10,000 units, preferred between 0.05 and 1000 units, and more preferably between 0.1 and 200 units per gram of glucose are in the food.

It may be advantageous to the agent according to the invention an acceptor in for the purpose of the invention sufficient quantity. examples for close suitable acceptors a, but are not limited on, NAD +, NADP +, FAD +, vitamins, such. B. Vitamin C, Vitamin E or vitamin A (including mixtures from that).

A Composition according to the invention for the Preparation of capsules (for example, size 00) can be made up per capsule 370 mg of 5-D-fructose dehydrogenase (Activity 5-D-fructose dehydrogenase 90 units / mg) and 100 mg dicalcium phosphate consist.

at a combination agent in which both enzymes are used, could for example, a size 0 capsule for Example 250 mg 5-D-fructose dehydrogenase (Activity 5-D-fructose dehydrogenase 90 units / mg) and 20 mg glucose isomerase (Activity the glucose isomerase 1 GIU / mg) and 50 mg dicalcium phosphate.

One another example of a combination preparation with both of the above-mentioned enzymes for the production of capsules the size 00 can advantageously 370 mg of 5-D-fructose dehydrogenase (activity of 5-D-fructose dehydrogenase 90 units / mg) and 30 mg glucose isomerase (activity of glucose isomerase 1 GIU / mg) and 70 mg dicalcium phosphate.

The Invention may, for example, per dose unit between 10 and 5 Million units of 5-D-fructose dehydrogenase. In addition, suitable Additives are used in the required amount. The invention can additionally still contain glucose isomerase, per unit dose between 0.01 and 100,000 GIU (= glucose isomerase units).

The Invention can for medical and non-medical purposes, eg. As a drug, Medical device, food, dietary Food, nutritional supplements, balanced diet or food additive.

With the agents according to the invention the calorie content usable by the organism can be carbohydrate-containing Food can be reduced so much that a significant weight reduction achieved or despite consumption of high-carbohydrate food weight gain can be prevented. Thus, the agents of the invention for use in methods of therapeutic treatment of the human or animal body suitable in which limit or reduce the intake is aimed at from carbohydrate-derived dietary calories, z. As in the therapy of diseases of the cardiovascular system (eg hypertension, coronary heart disease, venous insufficiency, heart failure, left ventricular hypertrophy), metabolic and hormonal function (eg diabetes mellitus Type II, dyslipidemias, hyperuricemia, Hyperlipoproteinemia) respiratory system (eg, sleep apnea, Pickwick syndrome); hepatobilliären System (eg fatty liver, cholecystolithiasis), the musculoskeletal system (eg gonarthrosis, heel spurs, ankle osteoarthritis), the skin (eg, Intertrigo, Hirsutimus, Striae), the subject of neoplasia (eg increased Risk for Endometrial, breast, cervical, gallbladder carcinoma, etc.), the therapy of disorders the sexual function (eg reduced fertility, complications at birth) and in the treatment of psychosocial problems (eg Self-confidence, social isolation, discrimination, partner and professional problems) and other problems, such. B. a reduced mobility and perseverance, increased Operation risk and difficult examination conditions. All these Diseases and health problems are common Associated with obesity.

The agents according to the invention are especially for use in obesity and therapeutic Treatment of obesity suitable.

Claims (32)

5-D-fructose dehydrogenase for use in the medicine. 5-D-fructose dehydrogenase as a drug. Medicament containing a 5-D-fructose dehydrogenase 5-D-fructose dehydrogenase in combination with glucose isomerase for use in medicine 5-D-fructose dehydrogenase in combination with glucose isomerase as a medicine. Medicament containing 5-D-fructose dehydrogenase in combination with glucose isomerase. Medicament according to one or more of claims 1 to 6, to be suitable or determined to be used orally. Medicament according to one or more of claims 1 to 7, suitable or intended food before consumption or already added during production. 5-D-fructose dehydrogenase as a medical device. 5-D-fructose dehydrogenase in combination with glucose isomerase as a medical device. Medical device containing a 5-D-fructose dehydrogenase. Medical device containing a 5-D-fructose dehydrogenase and a glucose isomerase. Food containing a 5-D-fructose dehydrogenase. Food containing a 5-D-fructose dehydrogenase and a glucose isomerase. Food according to claim 13, containing the 5-D-fructose dehydrogenase in an amount effective to convert fructose to glucose. Food according to claim 14, containing the 5-D-fructose dehydrogenase in an amount effective to convert fructose to 5-keto-D-fructose and the glucose isomerase in one to convert glucose to fructose effective amount. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase for the manufacture of a medicament, a medical device, a food, a dietary one Food, a dietary supplement, a food supplement or a balanced diet. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase in the therapy of obesity. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase for use in procedures for the therapeutic treatment of the human or animal body, where limiting or reducing the intake of carbohydrates aimed at nutritional calories, especially in the Therapy of obesity-related health problems and diseases, including Cardiovascular diseases Systems (eg hypertension, coronary heart disease, venous insufficiency, Heart failure, left ventricular Hypertrophy), metabolic and hormonal function (eg Type II diabetes mellitus, dyslipidemias, hyperuricemia, hyperlipoproteinemia), of respiratory system (eg sleep apnea, Pickwick's syndrome), of the hepatobilliary System (eg fatty liver, cholecystolithiasis), the musculoskeletal system (eg gonarthrosis, heel spurs, ankle osteoarthritis), the skin (eg, intertrigo, hirsutimus, striae) and especially in therapy Obesity associated with obesity (eg increased risk for endometrial, Mammary, cervical-gallbladder carcinoma, etc.), disorders the sexual function (eg reduced fertility, complications at birth), psychosocial problems (eg reduced self-confidence, social isolation, discrimination, partner and professional problems) and other problems, such. B. a reduced mobility and endurance, an increased risk of surgery and complicated examination conditions. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase for the manufacture of a product for use in the therapy of obesity. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase for the manufacture of a product for use in methods of therapeutic treatment of the human or animal body, where limiting or reducing the intake of carbohydrates aimed at nutritional calories, especially in the Therapy of obesity-related health problems and diseases, including Cardiovascular diseases Systems (eg hypertension, coronary heart disease, venous insufficiency, Heart failure, left ventricular Hypertrophy), metabolic and hormonal function (eg Type II diabetes mellitus, dyslipidemias, hyperuricemia, hyperlipoproteinemia), of respiratory system (eg, sleep apnea, Pickwick syndrome); hepatobilliären System (eg fatty liver, cholecystolithiasis), the musculoskeletal system (eg gonarthrosis, heel spurs, ankle osteoarthritis), the skin (eg Intertrigo, Hirsutimus, Striae) and in the therapy of with Adiposity associated with neoplasia (eg increased risk of endometrial, Mammary, cervical-gallbladder carcinoma, etc.), disorders of sexual function (e.g. B. reduced fertility, Complications at birth), psychosocial problems (eg diminished self-confidence, social isolation, discrimination, partner and professional problems) and other problems, such. B. a reduced mobility and perseverance, increased Operation risk and difficult examination conditions. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase to reduce bioavailability of fructose and glucose in the human or animal organism. Use of 5-D-fructose dehydrogenase to reduce the content of fructose in a food. Use of 5-D-fructose dehydrogenase in combination with glucose isomerase for reducing the content of fructose and Glucose in a food. Use of 5-D-fructose dehydrogenase alone or in combination with glucose isomerase to reduce the recoverable Calorie content of the food. Use according to one or more of claims 18 to 25 as a medicine, medical device, food, dietary Food, nutritional supplements, Food additive or as a balanced diet. Use according to one or more of claims 18 to 25, wherein the enzyme or enzymes are in the form of a product and this product is a pharmaceutical, medical device, foodstuff, diä dietary supplement, dietary supplement, food supplement or balanced diet. Use according to one or more of claims 17 to 27, the agent being suitable or intended to be applied orally to become. Use according to one or more of claims 17 to 28, the means being suitable or intended to be the food be added before consumption or already during production Use according to one or more of claims 17 to 27, wherein the product is suitable or intended, in immobilized Shape to be used. Process for treating a food, characterized by adding a food with a 5-D-fructose dehydrogenase in a manner in which the effect of the enzyme first after eating the food. Process for treating a food, characterized by adding a food with a 5-D-fructose dehydrogenase and a glucose isomerase in a manner in which the Effect of enzymes only after eating the food begins.