DE102006014424A1 - Use of glucose isomerase in combination with 5-D-fructose dehydrogenase and an enzyme, e.g. invertase, for producing a pharmaceutical composition for preventing, treating, or diagnosing diabetes - Google Patents

Abstract

Use of glucose isomerase in combination with 5-D-fructose dehydrogenase and optionally one or more of invertase, lactase, maltase, alpha -amylase, beta -amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase (CGTase) for the production of an agent, preferably a pharmaceutical composition, for preventing, treating, or diagnosing diabetes. Use (M1) of glucose isomerase in combination with 5-D-fructose dehydrogenase and optionally one or more of invertase, lactase, maltase, alpha -amylase, beta -amylase, glucoamylase, pullulanase, isoamylase, amyloglucosidase, or cyclomaltodextrin glucanotransferase for the production of an agent, preferably a pharmaceutical composition, for preventing, treating, or diagnosing diabetes; for reducing the bioavailability of glucose and/or fructose in humans or animals; for reducing the glucose and/or fructose content in a foodstuff; or for preventing, or at least reducing, an increase of the level of blood glucose after the intake of glucose containing food. Independent claims are included for the following: (1) a process for the treatment of a foodstuff comprising contacting the foodstuff with enzymes as in (M1) and initiating the reduction of the glucose and/or fructose content of the foodstuff; (2) a mammalian-ingestible composition (C1), which comprises enzymes that collectively convert D-glucose into a form that is biologically inactive, not digestible in the digestive tract and/or not metabolizable in a mammalian body; (3) microencapsulated glucose isomerase (MGI); (4) a kit comprising (C1) and instructions explaining how to use the enzymes to reduce the effects of glucose in the mammalian body; (5) a reduced-total glucose foodstuff; (6) a method (M2) for preparing a reduced-total glucose foodstuff comprising contacting a foodstuff or its precursor with (C1); and (7) a method (M3) for preparing a foodstuff or foodstuff precursor having a reduced effective glucose content comprising contacting a foodstuff or its precursor with (C1) where the enzymes are incorporated so that they will convert the D-glucose to the first form after ingestion of the foodstuff.. ACTIVITY : Antidiabetic. No biological data given. MECHANISM OF ACTION : None given.

Description

object The invention is an agent for use in diabetes which reduces the glucose content of food and other consumed substances. In this case, the term "diabetes" in the sense of this patent application all Distorted forms Blood sugar metabolism, also of a lighter kind, including all Forms of diabetes, such as Diabetes I including LADA diabetes (latent autoimmune diabetes in adults), diabetes II and gestational diabetes Understood. Accordingly, the invention is also suitable for persons whose blood sugar metabolism only slightly disturbed is, so she (yet) not to be referred to as a diabetic in the medical sense.

Under containing glucose for the purposes of this patent application all substances and understood foods which are either glucose in pure form contain or released from glucose in the digestive tract can be, such as from sucrose. This is going through in the intestine enzymatic cleavage of glucose and fructose released in equal parts.

diabetes is a very common problem and the incidence of diabetes has risen steadily in Western Europe and North America. The two main forms are type 1 diabetes (about 5-10%) and type 2 diabetes (about 90%). For example, in the Federal Republic Germany over 6 million people have diabetes and about another 3.9 Millions of people at a so-called disturbed glucose tolerance. The consequences Diabetes is an increase in blood glucose concentration, a Glucosuria and later Consequences of the increased Blood glucose concentration in different organ systems, lipid metabolism disorders, etc. Depending on whether it is due to the long-standing too high average Blood glucose levels caused a variety of damage, such as on eyes, kidneys and nerves, or acts caused by short-term blood sugar spikes damage such as. a premature wall damage of the great arterial Vessels, speaks one of micro or macroangiopathic sequelae.

The List of possible Complications and diabetic late damage is long and these are well documented in the literature The previous therapies at Blood glucose metabolism disorders restrict In essence, to increase the insulin content in the blood (through the feeding of insulin or by strengthening the insulin distribution) or to increase insulin activity. Another way is in the delay the absorption of carbohydrates (absorption retardants) with the consequence of abdominal Complaints of bacterial degradation in the lower intestinal sections getting carbohydrates. Despite all treatment options found so far Diabetes continues to be a need for gentle, gentle remedies Increase the blood sugar level due to the intake of glucose-containing food and prevent or reduce substances.

One Means that would reduce the amount of glucose absorbed would be so a very widespread and for decades existing urgent desire Satisfy, since those affected despite the variety of available Medicines and especially for Diabetics offered glucose-free dietary foods, considerable Difficulties with the "individual Setting ", i. with the exact tuning of the insulin dose to the carbohydrate intake, and are also very limited in the choice of food consumed. Such a remedy would also the overcoming a prejudice established in the professional world and in those affected, namely, that one Low carbohydrate diet complied must and must a significant change in dietary habits necessary be, mean and also a very significant improvement and leaps and bounds To further develop the therapy and nutritional options in diabetes. 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 diabetes. 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 which significantly reduces the usable glucose content of the diet, especially to take usually glucose-containing foods even in diabetes, without this leading to negative health consequences. Further It is the task of the invention to make diabetic foods accessible so far, because of their glucose content, they consume you were denied or their consumption for those with negative health consequences. Furthermore, a means be provided, which after ingestion of glucose at Diabetes related adverse health effects decrease or can prevent. Another object of the invention is a means available which increases blood glucose concentration Diabetes diminished after consumption of glucose-containing food or prevented.

The subject of the invention is therefore an agent which can solve all the problems described above. The agent contains 5-D-fructose dehydrogenase (syn. Fructose 5-dehydrogenase) and glucose isomerase (syn. Glucose-6-phos phat isomerase).

The Enzyme 5-D-fructose dehydrogenase causes the conversion of fructose to 5-keto-D-fructose. The enzyme glucose isomerase causes the conversion from glucose to fructose and vice versa. This arises - depending on present temperature - a Equilibrium with about 50% glucose and 50% fructose. A 5-D-fructose dehydrogenase For the purposes of this invention, an enzyme which is a dehydration of Fructose to 5-keto-D-fructose catalyze and a glucose isomerase in the context of this invention is an enzyme capable of converting glucose into fructose.

The effect according to the invention the enzyme combination is explained using the example of the starch. Because of strength during the Digestion especially glucose is released as a monosaccharide, This is converted by the glucose isomerase in fructose, which then by the 5-D-fructose dehydrogenase in the body non-utilizable 5-keto-D-fructose is converted. 5-D-fructose dehydrogenase prevents the balance described above from occurring can. Therefore, the glucose isomerase is glucose in fructose, which in turn is derived from 5-D-fructose dehydrogenase in 5-keto-D-fructose dehydrates, convert until there is no more glucose in the diet or the chyme is present.

Also with sucrose can be achieve a glucose reduction with this 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 is then try to balance the resulting imbalance, in which converts glucose to fructose. This conversion process will again continue until no more glucose in the chyme is available. It is possible, that until then part of the for The organism has been readily absorbed by readily available glucose is. However, the amount of total sugars Meal absorbed glucose with the aid of the present invention be significantly reduced. Depending on how high the enzyme activity per dose unit and how high the glucose content of each meal is the amount of glucose that the body absorbed, influence. According to the invention, if desired, also accomplish a complete or almost complete elimination of glucose.

The Invention is thus based on the fact that in the consumed carbohydrates, such as. Sucrose, contained or released from these in the intestine Glucose by the same or at least timely ingested Mixture of the two enzymes glucose isomerase and 5-D-fructose dehydrogenase by converting the glucose into fructose and its subsequent dehydration to 5-keto-D-fructose for the unwanted Absorption from the intestine into the bloodstream is no longer available. The enzymes will convert glucose to fructose and convert it to 5-keto-D-fructose until no Glucose is more present. The dosage of the added Enzymes so chosen be that even when feeding larger quantities In glucose, the reaction can proceed fast enough.

The has enzyme combination according to the invention Furthermore also the effect desired in diabetes the reduction of calorie intake, since the enzyme combination, such as Carbohydrates contained in the diet described above in indigestible 5-keto-D-fructose transforms. Especially in type II diabetes, this is desirable since those affected frequently overweight, High blood pressure and lipid metabolism disorders suffer.

object the invention is therefore a means for use in diabetes, which contains a glucose isomerase and a 5-D-fructose dehydrogenase.

object The invention further relates to an agent which is obtained by means of a glucose isomerase in combination with a 5-D-fructose dehydrogenase bioavailability reduced by glucose in the human or animal organism.

object The invention is also a means for reducing the recoverable Glucose content of the diet, which is a glucose isomerase in combination containing a 5-D-fructose dehydrogenase.

object The invention is also a means for preventing or reducing an increase in blood glucose concentration in diabetes after Consuming glucose-containing food.

One Another object of the invention is the use of a glucose isomerase in combination with a 5-D-fructose dehydrogenase in diabetes and diabetes related health problems and Diseases.

According to the invention, a 5-D-fructose dehydrogenase in combination with glucose isomerase too to reduce the usable glucose content in a food be used. Among the foods for the purposes of this invention include other also dietary Food, nutritional supplements, balanced diets and food additives.

The Invention allows glucose to be in a particularly simple manner To transform food into a form that does not lead to an increase in blood glucose concentration. The Invention allows thus also such foods for consumption by diabetics accessible make because of their glucose content so far avoided by those affected had to be.

According to the invention is further 5-D-fructose dehydrogenase in combination with glucose isomerase for Use in medicine, for example as a medicine. The invention accordingly also relates to a product which from 5-D-fructose dehydrogenase in combination with glucose isomerase or 5-D-fructose dehydrogenase in combination with glucose isomerase in addition to one or more other active ingredients, for Application in a medical procedure, in particular a method for the therapeutic treatment of the 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 for curing, relieving, to prevent or to recognize.

According to one In another aspect, according to the invention, a foodstuff is provided, 5-D-fructose dehydrogenase in combination with glucose isomerase contains. Furthermore, according to the invention a food provided that 5-D-fructose dehydrogenase in combination with glucose isomerase in one effective for reacting fructose to 5-keto-D-fructose Amount and glucose isomerase in one for converting 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 in combination with glucose isomerase is brought into contact under such conditions, among which the 5-D-fructose dehydrogenase can dehydrogenate fructose to 5-keto-D-fructose and the glucose isomerase can convert the glucose to fructose. One such food has one compared to otherwise untreated Foods reduced glucose content and is therefore suitable first for consumption in diabetes. Particularly advantageous may be Food produced by a process in which the Foods with a 5-D-fructose dehydrogenase in combination is added with a glucose isomerase in a manner in which the effect of the two enzymes only after the consumption of the food starts. Such 5-D-fructose deoxygenase and glucose isomerase containing food has the same taste as a Untreated food and is due to after eating for the first time for consumption Suitable for diabetes.

According to one Another aspect is according to the invention 5-D-fructose dehydrogenase in Combination with glucose isomerase provided as a medical device. The invention accordingly also relates to a medical device, from 5-D-fructose dehydrogenase in combination with glucose isomerase or 5-D-fructose dehydrogenase in combination with glucose isomerase contains one or more 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 combined yet with glucose isomerase in the medical-pharmaceutical field, in particular used in diabetes in humans or animals. Consequently acts it is the invention presented here to the first medical Indication for the combination of both enzymes. Both enzymes became common not yet for the therapeutic treatment of the human or animal body or for diagnostic Purposes used on the human or animal body.

The composition according to the invention can be taken orally before meals, at mealtimes or immediately thereafter so that it can develop its dehydrating effect on fructose in the dietary pulp. Preferably, the agent according to the invention is taken immediately before meals during meals or immediately after meals. The agent according to the invention may contain the enzymes without further additives contain. However, it is preferred that the agent of the invention further contains pharmaceutically acceptable and / or food safe additives, such as extenders, binders, stabilizers, preservatives, flavorings, etc. Such additives are for the preparation of medicines, medical devices, foods, dietary foods, nutritional supplements and Food additives are common and well known, and those skilled in the art know which additives are suitable in which quantities for certain dosage forms. The agent according to the invention particularly preferably contains as additives di-calcium phosphate, lactose, modified starch, microcrystalline cellulose, maltodextrin and / or Fibersol.

The inventive agent can also be added to a food before consumption. It can even target the food even in the making be added, its effect only after the consumption of the food to unfold. this could optionally, e.g. be achieved by a microencapsulation. This would the usable glucose content of the food to particularly advantageous Way without disadvantages for its taste is reduced. Therefore, preparations are preferred containing 5-D-fructose dehydrogenase and glucose isomerase, the this enzyme first in the digestive tract of a human or animal release or otherwise take effect, in particular in the stomach or small intestine. The invention could therefore, for example, in the preparation of desserts, fruit preparations (for example applesauce), jam, honey, chocolate and chocolate products, Baked goods (for example, cookies 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 (e.g., tomato ketchup) and fructose-containing sweeteners. For food that is cooked or baked, the inventive agent could after cooling e.g. mixed or sprinkled.

The inventive agent can also be added to a food to its effect after consumption of food derived from another food Unfold glucose. An example of this would be the addition of the agent according to the invention to a spread, so that the reduction contained in the bread utilizable glucose enters after consumption of the bread, without the Affect the taste of the bread. Further examples would be spice mixtures and mayonnaise for the use with French fries.

The inventive agent can also be used in immobilized form. This is special appropriate for Treat liquid Food, for example, can the enzymes are embedded in a glucose-permeable matrix: when a glucose-containing liquid Food is passed along the enzyme-containing matrix, then the food becomes glucose under the action of the enzymes withdrawn and converted to 5-keto-D-fructose.

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

The Invention can be in any for formulated the intended route of administration suitable form be. For the oral administration is preferably the agent according to the invention in Form of capsules (coated or not covered), Tablets (coated or not covered), Capsules, the coated ones or uncoated Pellets, granules or micro or minitablets containing tablets, the from plated or uncoated Pellets, dragees or micro- or minitablets are pressed, Gel caps or in liquid Shape as a solution, drop, Suspension or gel formulated. The invention may also be described as dried oral supplement or moist oral supplement available. The formulation of the agent according to the invention is suitable as a powder especially for adding to a food. The powder can be sprinkled on a meal, or it can be a porridge or a drink be mixed. It is particularly useful if that as a loose Powder offered in individual dosing quantities, such as in individual bags or capsules, or when it is provided in a dosing dispenser. Very particularly preferred is the agent of the invention formulated as a powder or granules in capsules or as a tablet, which are administered orally.

to Oral administration may include the active ingredient 5-D-fructose dehydrogenase 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 or for use in manufacture a food which delivers the active ingredient to its site of action and the receiver Human or animal will not cause significant harm. The concrete form of the carrier is not crucial.

The total amount of carrier and / or excipient for a 5-D-fructose dehydrogenase and glucose isomerase-containing agent is preferably between 5 and 99.9 wt.%, More preferably between 10 and 95 wt.% And even more preferably between 25 and 90% by weight of the composition Zung.

suitable Excipients and / or carriers include 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 shut down Calcium carbonate, magnesium stearate, maltodextrin, di-calcium phosphate, modified starch, 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 of certain dosage form, e.g. 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 is delayed at low pH values. It is possible, too 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 polymethylmethacrylate (PMMA), e.g. Eudragit (Röhm GmbH, Darmstadt), in particular Eudragit FS30D and Eudragit L30D-55. By the addition from e.g. Sodium hydroxide to the coating agent Eudragit, the pH resistance of this coating agent can be additionally influenced. 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 being hereby incorporated by reference.

Other suitable compatible 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, stabilization methods include and method 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 on fermentation technology Pathways using suitable microorganisms (bacteria, molds, Yeasts). The tribes will be taken from natural ecosystems according to a special screening program, as pure cultures isolated as well as 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 is usually produced microbiologically using the microorganism Gluconobacter industrius. The glucose isomerase is likewise commercially available (for example Novozymes A / S, Denmark) and is usually microbiologically produced with the aid of the microorganism Streptomyces murinus. However, the invention is not limited to the currently commercially available enzymes, but generally relates to enzymes that can cause the conversion of fructose - specific or unspecific - to 5-keto-D-fructose or glucose - specific or nonspecific - to fructose , The person skilled in the art can prepare suitable further enzymes by customary methods, for example by mutagenesis of the gene for 5-D-fructose dehydrogenase present in Gluconobacter industrius or by mutagenesis of the gene for glucose isomerase present in Streptomyces murinus. The enzymes can also be produced with the aid of other microorganisms, such as fungi, in sufficient quantities and with the required purities, also using the genetic engineering methods customary today. Should it be desired, for example, the enzymes with other microorga The genetic information of a microorganism initially found by a comprehensive screening, which has also proved to be a suitable source of the enzyme with the desired properties, could be transferred to one of the microorganisms usually used for enzyme production. It is also possible to modify the enzyme or enzymes themselves and to produce the enzyme (s) using the methods customary today in industrial enzyme development and enzyme production, such as genetic engineering. The use and manner of carrying out all of these processes for the development and production of the enzyme or enzymes in the desired purities and activities and with the desired properties are well known to those skilled in the art. The explanations in Chapter 2 (page 82-page 130) of the textbook "Food Biotechnology and 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 the amount of 5-D-fructose dehydrogenase that is Micromol D-fructose per minute at pH 4.5 and 37 ° C in 5-keto-D-fructose converted. In general, the activity of 5-D-fructose dehydrogenase per Dose unit between 10 and 5 million units, preferably between 25 and 2.5 million units, and most preferably between 50 and 1 million units.

The activity The glucose isomerase should generally be between 0.01 and 100,000 GIU, preferably between 0.05 and 10,000 GIU and more preferred between 0.1 to 1,000 GIU per dose unit. One unity This enzyme is defined as glucose isomerase unit (GIU), which at a pH of 7.5 and a temperature of 37 ° C from a initially 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 in very different types of diabetes in their most diverse Severity is used. In addition, the different arise Dosages also in that, depending on the particular Food strongly varying amounts of glucose are supplied.

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), Amyloglucosidase, alpha-amylase, Beta-amylase, glucoamylase, pullulanase, isoamylase, cyclomaltodextrin glucan transferase (CGTase). These enzymes have the property alone or in Combination with other enzymes, glucose from glucose-containing substances and foods, the enzymes being pullulanase and isoamylase also affects the effectiveness of glucoamylase and beta-amylase increase.

For example For example, the invertase can produce glucose from e.g. Sucrose and the lactase glucose release from lactose. Beta-amylase breaks down e.g. 1,4-alpha bonds in starch from non-reducing end of the polysaccharide chain with elimination of Maltose and by action of maltase on maltose becomes glucose released. By adding one or more of these enzymes to the agent according to the invention So may the body's release of glucose from glucose-containing substances or foodstuffs, in particular made of sucrose and starch, supports and accelerated, so that by the glucose isomerase caused conversion of glucose to fructose take place more rapidly can. Therefore would be by the addition of one or more of these enzymes to the agent according to the invention advantageously also a reduction of the required amount of glucose isomerase possible. Alles these enzymes are commercially available (e.g., BioCat Inc., Troy, USA or Novozymes, A / S, Denmark or Amano Enzymes Inc., Japan) and found so far in combination with glucose isomerase and 5-D-fructose dehydrogenase never Application in the medical-pharmaceutical field, in particular not in diabetes.

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 glucose per gram of glucose in the food and glucose isomerase activity between 0.01 and 10,000 GIU, preferably between 0.05 and 1,000 GIU, and more preferably between 0.1 and 200 GIU per gram of glucose lie 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 suitable Close acceptors a, but are not limited NAD +, NADP +, FAD +, vitamins, e.g. Vitamin C, Vitamin E or vitamin A (including Mixtures thereof).

An agent according to the invention in capsules (eg size 3) could, for example, 55 mg per capsule 5-D-fructose dehydrogenase (activity of 5-D-fructose dehydrogenase 1000 units / mg), 50 mg glucose isomerase (activity of glucose isomerase 1 GIU / mg) and 55 mg dicalcium phosphate.

One Another composition example for the production of capsules (e.g., size 00) could be per Capsule 165 mg 5-D-fructose dehydrogenase (activity of 5-D-fructose dehydrogenase 1000 Units / mg), 150 mg glucose isomerase (activity of glucose isomerase 1 GIU / mg) and 155 mg dicalcium phosphate.

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

The Invention can for medical and non-medical purposes e.g. as a medicine, medical device, Food, dietary Food, nutritional supplements, balanced diet or Food additive be provided.

With the agent of the invention can through Diabetes of varying severity caused discomfort and health problems be significantly reduced or eliminated. The presented here Invention is particularly for the therapeutic treatment of diabetes suitable. It is also for use in therapeutic procedures Treatment of the human or animal body suitable in which an uncontrolled Rise in blood sugar levels should be prevented or a Lowering the blood sugar level is sought.

Claims (20)

Glucose isomerase in combination with 5-D-fructose dehydrogenase for use in medicine. 2-glucose isomerase in combination with 5-D-fructose dehydrogenase as a drug. Medicaments containing glucose isomerase in combination with 5-D-fructose dehydrogenase. Medicament according to one or more of claims 1 to 3, to be suitable or determined to be used perorally. Medicament according to one or more of claims 1 to 4, suitable or intended food before consumption or already added during production. Glucose isomerase in combination with 5-D-fructose dehydrogenase as a medical device. Medical device containing a glucose isomerase and a 5-D-fructose dehydrogenase. Food containing a glucose isomerase and a 5-D-fructose dehydrogenase. Food according to claim 8 containing the glucose isomerase in an amount effective to convert glucose to fructose, and the 5-D-fructose dehydrogenase in an amount effective to convert fructose to 5-keto-D-fructose. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase 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 glucose isomerase in combination with 5-D-fructose dehydrogenase in the therapy of diabetes. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase for the manufacture of a product for use in therapy or diagnosis of diabetes. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase to reduce bioavailability of glucose in the human or animal organism. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase for reducing the level of glucose in a food. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase for preventing or reducing an increase in blood glucose concentration in diabetes after eating glucose-containing food. Use of glucose isomerase in combination with 5-D-fructose dehydrogenase in diabetes. Use according to one or more of claims 11 to 16 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 11 to 16, wherein the enzymes are in the form of a product and that product is a medicinal product, medical device, foodstuff, dietary supplement, food supplement, food additive or a balanced diet. Use according to one or more of claims 10 to 18, the agent being suitable or intended to be administered orally to become. Use according to one or more of claims 10 to 19, the means being suitable or intended to be the food be added before consumption or already during production Process for treating a food, characterized by adding a food to a glucose isomerase and a 5-D-fructose dehydrogenase in a manner in which the action of the enzymes first after eating the food.