EP1624887A1 - One or several enzyme-containing compounds, dietetic food products and drugs produced from said compounds and the use therefor for medical purposes - Google Patents

Abstract

The invention relates to one or several enzyme-containing compounds, i.e. to one or several hydrolyses and to one or several antioxidants which are selected from ubiquinones, carotinoides and antioxidative vitamins. The inventive compounds are used in the form of components for producing food products or drugs which are used, inter alia as dietetic food supplements, in particular for a supplementary dietetic regime and for treating immune system disorders.

Description

 "Enzyme-containing compositions, dietetic foods and pharmaceuticals made therefrom and their use for medical purposes"

The present invention relates to the field of enzyme-containing compositions and to foods, in particular dietary food supplements which are used, inter alia, as a supplementary balanced diet, and to medicaments which contain these enzyme-containing compositions or consist of these enzyme-containing compositions. It relates more specifically to enzyme-containing compositions, foods and pharmaceuticals which contain hydrolases and other medically active ingredients, and their use, inter alia. for all diseases that result from dysregulation of the immune system, both through internal and external influences.

In the sense of the present invention, a balanced and supplementary balanced diet is understood to mean a food that is taken by patients under medical supervision for certain medical purposes for the treatment of diseases.

Dietary supplements are foods that are offered in the form of tablets, capsules or as a powder. They serve to supplement the food with certain substances, such as vitamins, minerals, trace elements and fiber. For this purpose, these substances are usually contained in an increased concentration. Dietary nutritional supplements are products that themselves have only a low average calorific value and nutritional value and can therefore also be taken as part of a diet.

Dietary supplements support healthy people every day to improve their diet, for example because of their rhythm of life they are unable or unable to find the time to take all the necessary nutrients to a sufficient extent with normal food.

Dietary supplements can also compensate for deficiencies that are caused by a disease or the treatment of a disease. The therapy result and the quality of life of the patient can be improved by the targeted compensation of a lack of essential micronutrients and / or protective food ingredients with (e.g. dietary) food supplements, which is often no longer possible with normal food in various diseases. Dietary supplements can thus generally improve the health of users and have a positive effect on the course of the disease and the success of treatment in sick people.

Dietary supplements are generally not drugs. However, depending on the area of application, the ingredients selected and their dosage, they can also be drugs.

The invention relates to special compositions which contain the active ingredients intended for food supplementation and the foods and medicaments obtainable therefrom which may additionally contain auxiliaries, for example for the pharmaceutical formulation. These compositions, foods or pharmaceuticals improve the supply of healthy and sick people with essential nutrients, while in the case of sick people it also increases the success of therapeutic treatment.

Enzyme-containing preparations are known in the prior art. WOBE-Mugos ^® contains trypsin, chymotrypsin, papain and thymus extract. It is used, among other things, in long-term supportive treatment for malignant tumors. Wobenzym ^® contains a mixture from animal enzymes from pancreas and vegetable enzymes from pineapple comosus and caica papaya as well as rutoside. It is used in the supportive treatment of inflammation and vascular diseases.

Starting from this prior art, it is an object of the present invention to provide compositions, foods and pharmaceuticals with a modified chemical composition which have an improved effectiveness as health-promoting foods, for example in the form of nutritional supplements, and as pharmaceuticals in the medical field and for new ones Uses or indications are useful.

According to a first aspect, the invention relates to compositions which contain one or more hydrolases and one or more antioxidants which are selected from vitamins, carotenoids, selenium-containing substances, ubiquinones and which have an antioxidant effect.

Hydrolases are enzymes that hydrolytically cleave ester, ether, peptide, glycoside bonds, etc. These include the esterases, phosphate ases, glycosidases and the proteases which can be used according to the invention. In addition to the naturally occurring hydrolases obtained from natural products, hydrolases that are artificially, e.g. genetically engineered. Industrial hydrolases can be obtained from plants, animal organs, bacteria (proteases e.g. from Breυibacteήum linens) and fungi. Genetic engineering is obtained using bacteria or other microorganisms. The hydrolases can be used individually or in a combination of several hydrolases. Examples of hydrolases which can be used according to the invention are given below.

Even in low concentrations, antioxidants prevent or delay the oxidative destruction of active ingredients. In the human body They protect against cell damage and have anticarcinogenic effects. The antioxidants can be used individually or in a combination of several antioxidants. Examples of antioxidants from the classes of the antioxidant vitamins, carotenoids, selenium-containing substances and ubiquinones which can be used according to the invention are given below.

The combination of one or more hydrolases with one or more antioxidants gives compositions which have an increased health-promoting effect beyond the action of the individual substances, both on healthy and on sick people, in particular on people who suffer from dysregulation of the immune system Suffer. These include chronic or acute immune deficiency, impairment of the body's defenses, inflammatory rheumatic diseases and all other inflammatory, immunological and tumor diseases. For the treatment, the composition can be used in the form of a dietetic food for the supplementary balanced diet. The health of sick people is strengthened through improved nutrition. The sick people can be rheumatism patients or immunocompromised people and in particular tumor patients who are undergoing therapy to combat the tumor. This therapy can involve surgery, chemotherapy and / or radiation therapy, during which the patient has an increased need for essential micronutrients and protective nutritional components.

Essential micronutrients are understood here to mean the antioxidants used according to the invention, such as vitamins, carotenoids, selenium-containing substances, ubiquinones, insofar as they have corresponding antioxidative effects. Protective food components include the hydro used according to the invention. read how to understand plant and animal proteases. The increased demand for these substances is covered by the compositions, foods and medicaments according to the invention.

The above compositions according to the invention can additionally contain one or more polyphenols, one or more flavonoids and / or one or more flavonoid-containing substances.

The compositions according to the invention listed above can also contain one or more amino acids and / or one or more polysaccharides.

According to a second aspect, the invention relates to compositions which contain one or more hydrolases and one or more amino acids. These compositions also have advantageous immunomodulatory properties.

According to a third aspect, the invention relates to compositions which contain one or more hydrolases and one or more polysaccharides which, like the compositions of hydrolases and amino acids, inter alia for improving the state of health, in particular improving the immune status, in the form of foods or Medicines can be administered. In both cases it was surprisingly found that these advantageous properties can also be achieved without the presence of antioxidants.

According to a further subject of the invention, compositions are provided which contain hydrolases in combination with amino acids and polysaccharides.

According to a fourth aspect, the invention also relates to the compositions which exclusively contain hydrolases as active constituents contain and are optionally combined with pharmaceutically acceptable or approved food additives.

Accordingly, the invention, the compositions (I) to (X), containing the following active ingredients or ^'consist of, are:

(I) hydrolases + antioxidants, namely vitamins and / or carotenoids and / or selenium-containing substances and / or ubiquinones; (II) composition (I) + polyphenols and / or flavonoids and / or flavonoid-containing substances;

(III) composition (I) or (II) + amino acids and / or polysaccharides;

(IV) hydrolases + amino acids; (V) hydrolases + polysaccharides;

(VI) composition (IV) + polysaccharides;

(VII) composition (IV) + polyphenols and / or flavonoids and / or flavonoid-containing substances;

(VIII) composition (V) + polyphenols and / or flavonoids and / or flavonoid-containing substances;

(IX) composition (VI) + polyphenols and / or flavonoids • and / or flavonoid-containing substances,

(X) hydrolases,

where the above information, e.g. “Amino acids” are to be understood as indications of classes of substances from which one or more representatives can be contained in the compositions according to the invention. Accordingly, “amino acids” means “one or more amino acids”, for example “L-arginine” or “L-arginine + L-cysteine "etc., and the same applies to all other specified substance classes.

The hydrolases are preferably vegetable proteases and / or animal proteases, which are made from natural products obtained that represent natural products themselves or are produced synthetically or genetically.

The plant proteases preferably consist of pure bromoline, pineapple extracts, pure papain and papaya extracts. They are used individually or in combination. Bromelain consists of several proteolytic enzymes, more precisely endopeptidases, which are found in both ripe and unripe pineapples (Ananas comosus) and are obtained from the stems of the fruit clusters. Bromelain has an anti-inflammatory effect. Papain is a proteinase obtained from the milk juice of immature papaya fruits. Papain and bromelain can be used particularly preferably in combination. The enzymes can, in pure form or in the form of plant extracts, insofar as they contain the plant proteases, i.a. in the form of pineapple extracts and papaya extracts. Also preferred is the use of ficin, which is obtained from figs, or of fig extracts, which, like papain and bromelain, is a cysteine proteinase.

The animal proteinases used according to the invention preferably consist of trypsin and / or chymotrypsin and / or pepsin (peptidyl peptide hydrolase). For example, trypsin is obtained from the acidic pancreatic juice of pigs by fractional precipitation in an aqueous environment and by activation of the trypsinogen in the slightly alkaline pH range. This produces a mixture of α-, β- and γ-trypsin, which can hydrolyze peptide, amide and ester bonds if the basic amino acids arginine and lysine are involved in these bonds. Chymotrypsin is produced from the acidic pancreatic juice of cattle by extraction in an aqueous medium and subsequent fractional precipitation. Chymotrypsin is converted into the active form in a slightly alkaline environment. Chymotrypsin is obtained in crystalline form through further technical processing steps (ultrafiltration, chromatographic purification) and can be used like this. The mixture of chymotrypsin A and B obtained hydrolyzes peptide, amide and ester bonds if the aromatic amino acids tyrosine, phenylalanine and trypotophan as well as leucine, methionine and glutamic acid are involved in these bonds. As a proteolytic enzyme, pepsin also cleaves circulating immunoglobulins of the IgG type, so that the IgG molecule breaks down into an Fc and a bivalent F (ab) 2 fragment.

Bromelain has a strong anti-edematous effect and can therefore eliminate swelling faster than other proteases. Trypsin is also anti-edematous. Trypsin and chymotrypsin have a major influence on blood clotting and thus on the flow properties of the blood. The combination of papain and trypsin enables a particularly strong reduction in C 1 Q binding (complement area of the immune system). The two proteases change this binding area so that no binding can take place. Inflammatory reactions are inhibited.

Bromelain and papain are potent splitters of immune complex compounds that are considered markers for a dysregulated immune system. Especially in autoimmune diseases and in oncological diseases (cancer), high immune complex concentrations are repeatedly measured. Eliminating them is a prerequisite for undisturbed macrophage activity.

All proteases act on the expression of so-called cell surface adhesion molecules. About these adhesion molecules u. a. the communication between cells takes place. The modulation of the adhesion molecules is significantly improved by the combination of proteases.

The administration of single enzyme preparations (eg bromelain, alone) is far from having the therapeutic success as the administration of enzyme combinations. When combining bromelain with trypsin, ne superadditive effect with regard to the reduction of inflammation can be determined. This is shown in a significantly shorter healing phase when using enzyme combinations than is the case with monoenzyme preparations.

The combination of plant and animal proteases activates resting monocytes and NK cells, which stimulates the immune system. On the other hand, over-stimulated, over-activated immune cells are down-regulated by the enzyme combinations according to the invention.

These effects are particularly pronounced when the proteases are combined with antioxidants, in particular selenium-containing substances and especially sodium selenite, flavonoid-containing substances etc., amino acids and, if appropriate, polysaccharides.

Examples of compositions (X) preferred according to the invention are compositions which consist of bromelain and / or papain and / or trypsin and / or chymotrypsin, without other active ingredients, if appropriate in combination with pharmaceutically acceptable or food-approved auxiliaries, such as bromelain + papain + Trypsin + chymotrypsin.

Examples of other hydrolases which can be used according to the invention are: α-amylase, β-amylase, α-D-galactosidase, glucoamylase, lipases, proteinases, tannases, invertase, lysozyme, pullulanase, thioglucosidase, lactase, pectinolases, -L-rhamnosidase, the individually or in the form of mixtures, also with the above plant and animal proteases.

The hydrolases can be used over a wide range of concentrations. The lower limit corresponds to the concentration below which the desired health or therapeutic Effect no longer sets. The upper limit can be defined as the concentration from which there is no longer an increase in effectiveness and thus only the cost of the product.

The hydrolases such as bromelain and papain are preferably used in a total concentration of 20 to 60% by weight, more preferably 30 to 50% by weight, based on the total amount of active ingredients in the composition. If the composition contains two or more than two hydrolases, they are advantageously used in similarly large amounts, e.g. 25 wt% (or 15 wt%) papain and 25 wt% (or 15 wt%) bromelain. However, it is also possible for the hydrolases to be used in different concentrations, such as 15% by weight of animal protease (s) and 35% by weight of vegetable protease (s) and vice versa, or 15% by weight of a first vegetable protease , such as bromelain, and 35% by weight of a second plant protease, such as papain, or vice versa.

According to a preferred embodiment of the invention, the antioxidants consist of vitamins which are selected from vitamins A, C and E and the esters of vitamins A and E which can be used in foods and medicaments. Examples of such esters are the acetates, the aspartates and the tartrates.

Vitamin K, vitamin Bl (thiamine), B2 (riboflavin), B6 (pyridoxine), B 12 (cyano-cobalamin), niacin, pantothenic acid, biotin, folic acid, myo-inositol can be used as a support, but not themselves antioxidative Act. The vitamins from the B group all have coenzyme functions, so that their oral administration, in particular in combination with amino acids and / or polysaccharides, is physiologically advantageous.

The vitamins are used individually or in a mixture in the composition according to the invention. Their total concentration is, for example, in the range from 30 to 60% by weight, better still 40 to 50 % By weight, based on the active constituents of the composition, unless other antioxidants are used. If other antioxidants are included, the antioxidant vitamins can be used in lower concentrations.

The carotenoids, which are secondary plant substances, such as lycopene, a yellow-red plant pigment with a polyene structure, which is found in rose hip, tomatoes and other fruits, also have an antioxidative effect. Lycopene is a polyunsaturated polyene and has proven to be a very effective natural radical scavenger. It can therefore be used particularly advantageously in combination with the above-mentioned antioxidative vitamins. The combination with lycopene results in a surprisingly increased effectiveness in rheumatism therapy and the accompanying treatment in the context of cancer therapy. The proportion of the carotenoid, such as lycopene, as a component of the total amount of antioxidants is, for example, 5 to 20% by weight, based on the total amount of the active components, even better 9 to 16% by weight.

Further carotenoids which, like lycopene, can be used as antioxidants in the compositions according to the invention are α-, β-, γ-carotene, neurosporin, phytofluene, phytoene from the group of Caroline and xanthophyll, violaxanthin, crocetin, astaxanthin, capsanthin from the group the xanthophyll.

In addition, the compositions according to the invention can contain one or more flavonoids which are introduced in the form of pure flavonoids or in the form of natural products which contain flavonoids. Flavonoids belong to the class of polyphenols or plant phenols (PHP = polyhydroxyphenols).

According to the invention, the flavonoids can be selected from flavones, flavonols, flavanols, isoflavanols. In addition to quercetin, these include querceting glycosides such as rutin, the flavanones eriodictyol, Hesperetin, Liquiritigenin, Naringenin, Pinocembrin, the Flavanolol Taxifolin, the Flavone Apigenin, Chrysin, Diosmetin, Eupatorin, Luteolin, Scutellarein, Scutellareintetramethylether, Sinensetin and the Fla- vonole Axillarin, Chrysoplenetin, Euphanoline, Euphrine, Chrysoplenin, Chrysopetinin Gossypetin, isorhamnetin, jaceidin, camphor oil, myricetin, patuletin, quercetagenin, rhamnetin, robinetin, spinacetin.

Flavonoids which are particularly preferred according to the invention are: quercetin, hesperetin, pinocembrin, taxifolin, chrysin, luteolin, camphor oil, rhamnetin.

Onion powder, buckwheat extracts, grape seed flavonoids and citrus flavonoids come into consideration as the flavonoid-containing substance (s). The grape seed and citrus flavonoids contain oligomeric procyanidins (OPC), which belong to the group of flavonols. Standardized OPC contains at least 50% or more pine bark OPC (Pinus maritima) and grape seed OPC (Vitis vinifera). Grape seed OPC contains e.g. up to 20% catechin, epicatechin and epigallocatechin, pine OPC up to 10% catechin and up to 10% taxifolin. These oligomeric procyanidins can also be used in the compositions according to the invention because of their antioxidant activity.

Quercetin and the glycosides of quercetin, such as e.g. Rutin (rutoside). Rutoside is usually used as a venous agent, but, like the other flavonoids, also shows surprisingly good properties in the therapies according to the invention, i.e. the use as a balanced micronutrient in dietetic foods to strengthen the immune system, to strengthen the body's defenses, to treat inflammatory rheumatic diseases and to regulate the immune system in physical and / or psychological stressful situations.

The flavonoids and the flavonoid-containing natural products can be used individually or as a mixture of two or more of these substances. be applied. They are advantageously used in a concentration of 10 to 50% by weight, based on the total amount of active ingredients. Larger and smaller concentrations are also conceivable. When using grape seed flavonoids and pine bark, the daily dose can advantageously be 150 mg.

Very good results will be achieved in the accompanying treatment of cancer and rheumatism, but also in strengthening the body's immune system, if the compositions according to the invention additionally contain one or more antioxidative selenium-containing substances, such as selenium yeast and / or alkali metal selenite, such as sodium selenite. Alkaline earth metal selenites, such as magnesium selenite, ammonium selenite, which contain the corresponding selenates or selenamino acids (Se-methionine, Se-cystine). Selenium is an essential trace element. Naturally occurring, it is a component of glutathione peroxidase, thioredoxin reductase and thyroxine-5-deiodase. Selenium acts as an intracellular antioxidant. As a radical scavenger, it counteracts cell damage caused by radical formers or lipid hydroperoxides. Selenium modulates e.g. the function of lymphocytes and can increase the activity of natural killer cells. Selenium has one

Influences the DNA repair mechanism and can be involved in triggering apoptosis. In the compositions according to the invention it leads to a synergistic increase in the immunomodulatory properties of the compositions. According to the invention, selenium in its above compounds, as an essential trace element with an antioxidative effect, is an ideal combination partner with the antioxidants vitamin E and vitamin C.

Sodium selenite is particularly preferred. Sodium selenite (as well as other alkali metal and alkaline earth metal selenites) is very well absorbed after the administration, in particular oral administration, of a composition according to the invention due to its chemical structure, and it immediately develops the desired catalytic activity in the target cells. Accordingly, sodium selenite has a particularly good bioavailability and a particularly high biological activity. This is advantageous, for example, if a composition containing sodium selenite according to the invention is used to protect the healthy body cells of a cancer patient when performing chemotherapy or radiation therapy without delay and in a highly effective manner against the cell-damaging effects of chemotherapy / radiation therapy. The rapid bioavailability and the high biological activity of sodium selenite ensure that taking the composition according to the invention on the day of cancer therapy leads reliably to the desired cell protection in a short time. In contrast, the selenium methionine contained in selenium yeast must first be converted into the inorganic precursor before it can become active in the available selenium pool. The effects mentioned above occur with a time delay in selenium yeast. In addition, long-term administration of sodium selenite poses no risk of selenium accumulation in an inactive and possibly even harmful form.

After oral administration of sodium selenite, a significant reduction in interleukin 4 (IL-4) and a significant increase in the cytokine IFN-γ in the serum can be measured in test subjects. Furthermore, significant changes in the immune status can be determined after oral administration of sodium selenite: The CD8 + T cells decrease significantly. The disturbance of the immune balance, which is always present in chronic diseases, can be modulated in the direction of immune homeostasis by sodium selenite. There is a detectable balance between T-helper cells of type 1 (Thl), T-helper cells of type 2 (Th2), cytotoxic T cells and CD8 + - cytotoxic T cells.

Hydrolases, more precisely proteases, in particular combinations of protases, such as bromelain + papain or bromelain + papain + trypsin and / or chymotrypsin, improve the immunomodulatory properties of sodium sele- nit. The one-sided high stimulation of the immune system with a resulting imbalance of the various immune system parameters can be prevented by the simultaneous administration of sodium selenite together with proteases. This positive synergistic effect can be used for all chronic diseases and tumor diseases.

The selenites can be contained in a concentration of 0.001 to 0.3% by weight, better 0.01 to 0.1% by weight, based on the total amount of active constituents. A daily therapy dose of 50 to 300 μg has proven to be particularly good.

Another group of substances which is used according to the invention in combination with the hydrolases or as a preferred additive in the other compositions according to the invention is the group of amino acids. Glycine, L-alanine, L-serine, L-threonine, L- Valine, L-leucine, L-isoleucine, L-aspartic acid, L-asparagine, L-glutamic acid, L-glutamine, L-arginine, L-lysine, L-hydroxylysine, L-ornithine, L-citru- llin, L-cysteine, L-cystine, L-methionine, L-tyrosine, L-phenylalanine, L-tryptophan, L-histidine, L-proline, L-hydroxyproline can be used individually or in combination, as well as their pharmaceutical and for Food acceptable esters and salts insofar as they form esters and salts.

Glycine, L-arginine, L-glutamine and L-methionine have proven to be particularly advantageous. Most preferred is L-arginine.

Amino acids also have a role in modulating the immune system. They influence the signal transmission (signal transduction) of the immune system via the path of cell surface and cytokine modulation as well as the influencing of the redox potential of the system. Arginine is involved in the synthesis of the polyamines. These in turn are significantly involved in cell division, DNA synthesis and cell cycle regulation. Arginine has about this mechanism also an effect on the proliferation of lymphocytes, the cytolytic capacity of macrophages and NK cells and on the cytokine level (IL1). Arginine is the most important endogenous metabolite for nitrogen monoxide (NO) and also has a strong influence on the hemodynamic situation. In acute and chronic diseases, including cancer, the cytokine TGF-ß is overexpressed. The amino acid arginine locally lowers overexpression of the cytokine TGF-ß at the site of the inflammation. This effect is also ensured by the combination according to the invention with proteases.

The concentration of the amino acids is advantageously in the range from 5 to 15% by weight, more preferably 7 to 12% by weight, based on the total amount of active constituents.

Because of their good immunomodulatory properties, the compositions according to the invention can furthermore consist of hydrolases and polysaccharides or preferably contain such polysaccharides in combination with antioxidants which include amylose, pustulan, dextran, amylopectin, cellulose, arabanes, arabinogalactan, fructans, glucans, such as beta-glucan, has mannans, glycogen, chitin, pectins, locust bean gum, tamarind seed gum, guar be selected individually or in a mixture, wherein ß-glucan particularly advantageous egg ^x GFC characteris tics.

They are preferably used in a concentration in the range from 5 to 10% by weight, based on the total amount of active constituents.

β-glucan stimulates macrophage activity and leads to an increase in the number of NK cells and T lymphocytes. As an immunomodulating substance, it thus represents an optimal combination partner for proteases, particularly in the compositions (III), (V), (VI), (VIII) and (IX) given above. To improve the function of the cells belonging to the immune system, the compositions according to the invention can additionally be mixed with minerals, such as potassium, calcium, magnesium, iron, zinc, manganese or germanium, each in the form of inorganic salts, salts of organic acids or organic Compounds that contain these metals in complex form. Zinc and manganese compounds act as coenzymes for the proteases and thus support the biochemical and physiological cell processes. Zinc is an essential trace element for protein and nucleic acid metabolism. It converts vitamin A into the active form in the cell. Zinc shows a clear synergistic effect with vitamin C. Germanium has a central role in the immune system, stimulates interferon synthesis and is important in all immunologically triggered diseases. Germanium is therefore important for all tumor diseases and rheumatic diseases.

According to the invention, the following active substances are particularly preferred from a medical point of view because of their advantageous spectrum of action: from the substance class of

Hydrolases: bromelain, papain, trypsin, chymotrypsin, individually or as a combination of two to four hydrolases,

Vitamins: vitamins A, E and C, individually or as a mixture of these vitamins, carotenoids: lycopene, α-, β-, γ-caroin, xantophyll, individually or as a mixture of these carotenoids,

• selenium-containing substances: sodium selenite,

• Flavonoids (polyphenols - PHP): hesperetin, naringenin, pinocembrin, taxifolin, chrysin, eupatorin, luteolin, chrysoplenetin, chrysoplenol, eupaletin, galangin, gossypetin, kämperol, quercetin, individually or in the form of a mixture

Amino acids: L-arginine, L-methionine, L-glycine, L-glutamine, individually or in combination, • Polysaccharides: arabans, fructans, glucans, mannans, amylopectin, individually or as a mixture of several polysaccharides

• Minerals / trace elements: potassium, calcium, magnesium, iron, zinc, manganese or germanium, individually or in combination.

The effect of these combinations of proteases, vitamins, amino acids and trace elements on the immune system is stronger than can be expected from the individual substances. The immune system homeostasis as a prerequisite for a balanced immune system can be achieved with the help of the compositions according to the invention after reactions of the immune system to acute or chronic disruptive factors, if the actuators of the immune system, the cytokines and the cell surface adhesion molecules are modulated and influenced from all sides become. This can only be achieved effectively in an acceptable time by the above combination of different immunomodulating substances.

Compositions according to the invention which have particularly advantageous properties are specified below. They have the following qualitative composition with regard to the active ingredients:

• papain, bromelain, lycopene, vitamin E acetate, vitamin A acetate and sodium selenite (see Example 1); • papain, bromelain, lycopene, vitamin E acetate, ß-carotene, grape seed flavonoids and sodium selenite (see Example 2);

• Papain, bromelain, ß-carotene, citrus flavonoids, L-arginine and ß-glucan (see Example 3).

• papain, bromelain, vitamin E acetate, buckwheat extract containing rutin, onion powder containing quercetin and L-arginine (cf. ex.

4);

These compositions according to the invention may also contain one or more animal proteases, e.g. E.g .: trypsin or chy motrypsin or pepsin; Trypsin + chymotrypsin; Trypsin + chymotrypsin + pepsin; Chymotrypsin + pepsin; Trypsin + pepsin.

The amounts given follow in Examples 1 to 4, which relate to the same compositions. The amounts in which these active constituents are contained in the compositions according to the invention are, as already mentioned above for the hydrolases, not critical. The lower limit is the amounts below which the desired effect is no longer ascertained. The upper limit for the respective active ingredient is the amount above which no increase in effect is observed.

The compositions according to the invention can be prepared by simply mixing the active ingredients and are then in the form of a powder. They can consist exclusively of the specified active ingredients or contain them in addition to customary auxiliaries. However, for the preparation of certain dosage forms, such as tablets, film-coated tablets with an enteric coating, capsules, dragees, effervescent tablets, suppositories, clysms, they are mixed with customary pharmaceutical auxiliaries. The following are used for this purpose: microcrystalline cellulose, talc, highly disperse silicon dioxide, stearic acid, magnesium stearate, magnesium oxide, fish gelatin, crosspovidone, calcium silicates, hydroxypropyl cellulose, hydroxymethyl cellulose and titanium oxide. The galenical preparation of the various dosage forms is not critical and is known in the prior art.

The present invention furthermore relates to foods, in particular for the supplementary balanced diet, to strengthen the immune defense or the body's defenses, to treat inflammatory and inflammatory rheumatic diseases, to regulate the immune system in physical and / or psychological stressful situations, to strengthen the Immune system before, during and / or after tumor-destroying treatment or for Reduction of the risk of tumor recurrences and secondary malignancies which contain one of the compositions according to the invention described above or, if no additives are used, consist of such a composition.

The present invention also relates to medicaments which contain or consist of a composition according to the invention as described above, for strengthening the immune defense or the body's own defenses, for treating inflammatory and inflammatory rheumatic diseases, for regulating the immune system in physical and / or psychological stressful situations, to strengthen the immune system before, during and / or after tumor-destroying treatment or to reduce the risk of tumor recurrences and secondary malignancies.

The invention also relates to the use of the compositions according to the invention for dietary treatment, in particular for the supplementary balanced diet, for strengthening the immune defense or the body's own defenses, for the treatment of inflammatory and inflammatory rheumatic diseases, for regulating the immune system in physical and / or psychological stressful situations, to strengthen the immune system before, during and / or after tumor-destroying treatment or for sen- Reduction of the risk of tumor recurrences and second malignancies.

As an example of the above uses, the accompanying therapy in the treatment of carcinomas is given, in which the composition given in Example 1 can be used. The composition and the foods that can be produced from it ensure a healthy and wholesome diet. This applies both to the period before, during and in defined periods after tumor destructive therapy, for example surgery, chemotherapy and / or radiation therapy. Those caused by nausea, decreased food intake, vomiting, diarrhea and sweating Reduced absorption of micronutrients caused (eg vitamins, trace elements) is compensated. This improves the patient's tolerance to the treatment, increases the response to the therapy and improves the patient's quality of life. The proteases reduce the side effects of the therapy, the lycopene shows prophylactic and therapeutic effects. For example, the reduction in the incidence and aggressiveness of prostate carcinomas was determined. Overall, the effectiveness of tumor destructive therapy is improved.

The administration of the defined balanced micronutrients such as vitamin A, vitamin E, sodium selenite, lycopene, bromelain and papain can be divided into two sections: a first section, which represents the active treatment phase, with an increased dose of the composition, on the a second section follows, in which a maintenance dose is administered over a period of 4 weeks. This is, for example, 50% of the dose of the active treatment phase.

Finally, the present invention relates to the use of the compositions according to the invention described above for the manufacture of medicaments for the above-mentioned and other indications.

Four examples of compositions according to the invention and their indications are given below.

In addition to the active ingredients, the compositions contain customary additives or auxiliaries for the formulation of foods or medicaments, namely microcrystalline cellulose, talc, highly disperse silicon dioxide, stearic acid. The quantities given are in milligrams, based on a single dose of the respective composition to be administered. Example 1: Composition for nutritional supplementation in tumor-destructive treatment

- Papain 50

- Bromelain 50

- Lycopene 25

- Vitamin E acetate 72

- Vitamin A acetate 3

Sodium selenite 0.042

microcrystalline cellulose 186

- talc 10.9

- highly disperse silicon dioxide 3

- stearic acid 10

The composition is used for supportive therapeutic treatment in tumor destructive treatments. The above composition is administered orally in the form of tablets a maximum of four times a day. It is administered in the form of a powder, coated tablet, tablet or film-coated tablet with an enteric coating.

Example 2: Composition for the treatment of inflammatory rheumatic diseases

- Papain 33

- Bromelain 34

- Lycopene 16

- Vitamin E acetate 48

- ß-carotene 5

- Grape seed bioflavonoid 33

Sodium selenite 0.028

microcrystalline cellulose 207

- talc 11.0

- highly disperse silicon dioxide 3.0 - stearic acid 10

The composition is used in the form of a food as a powder, dragee, tablet or film-coated tablet with an enteric coating for the supplementary balanced diet for the treatment of diseases in the rheumatic range. It is administered orally up to four times a day.

Example 3 Composition for strengthening the immune system

- Papain 33

- Bromelain 34

- ß-carotene 5

- Citrus bioflavonoid (45%) 33

- L-arginine HC1 16

β-glucan 9.0

microcrystalline cellulose 207

- talc 11.0

- highly disperse silicon dioxide 3.0

- stearic acid 10

The composition is administered in the form of a food as a powder, dragee, tablet or film-coated tablet with an enteric coating for the supplementary balanced diet to strengthen the immune system. It is given in one to four doses a day, each of which corresponds to the above dosage.

Example 4 Composition for the supplementary balanced diet for strengthening the immune system, strengthening the body's defenses and for the dietary treatment of inflammatory rheumatic diseases.

- Papain (papaya extract) 50

- Bromelain (pineapple extract) 50 - Vitamin E acetate 50

- Buckwheat extract (Rutin) 100

- Onion powder (quercetin) 50

- L-arginine HC1 25

Magnesium oxide 50

The composition is used in the form of a powder, dragee, tablet or film-coated tablet with an enteric coating as a food for strengthening the immune system. It is administered orally a maximum of four times a day.

Claims

claims 1. Composition containing one or more hydrolases and one or more antioxidants selected from vitamins, carotenoids, selenium-containing substances, ubiquinones, which have an antioxidative effect. 2. Composition containing one or more hydrolases and one or more amino acids. 3. Composition containing one or more hydrolases and one or more polysaccharides. 4. Composition containing one or more hydrolases, one or more amino acids and one or more polysaccharides. 5. Composition according to claim 1, characterized in that it contains one or more polyphenols, one or more flavonoids and / or one or more flavonoid-containing substances. 6. Composition according to claim 1 or 5, characterized in that it contains one or more amino acids and / or one or more polysaccharides. 7. Composition according to one of claims 2, 3 and 4, which contains one or more flavonoids and / or one or more flavonoid-containing substances. 8. Composition according to one of claims 1 to 7, characterized in that it is in the hydrolases or plant proteases and / or animal proteases. 9. The composition according to claim 8, characterized in that the plant (s) protease (s) is / are selected from bromelain, bromelain-containing pineapple extracts, papain, papain-containing papaya extracts and that the animal (s) protease (s ) is selected from trypsin and chymotrypsin. 10. Composition according to one of claims 1 and 5 to 9, characterized in that the antioxidant (s) vitamin (s) is selected from vitamins A, C and E and the esters of vitamins A and E. 11. Composition according to one of claims 1 and 5 to 10, characterized in that the antioxidant (s) selenium-containing substance (s) among selenium yeast, alkali metal selenites such as sodium selenite, alkaline earth metal selenites such as magnesium selenite or ammonium selenite, and the corresponding selenates is selected. 12. The composition according to any one of claims 5 to 11, characterized in that the flavonoid or flavones is selected from flavones, flavonols, flavanols, isoflavanols. 13. The composition according to claim 12, wherein the fla- vonoids are quercetin, rutin, hesperetin, pinocembrin, taxifoline, chrysin, lteolin, kämperol, rhamnetin. 14. The composition according to any one of claims 5 to 11, wherein the flavonoid-containing substance (s) is (are) selected from onion powder, buckwheat extracts, grape seed flavonoids and citrus flavonoids. 15. The composition according to any one of claims 1, 5, 6 and 8 to 14, wherein the ubiquinone is the coenzyme Q10. 16. The composition according to any one of claims 1, 5, 6 and 8 to 15, wherein the carotenoids are carotene, lycopene, neurosporin, phytofluene, phytoene, xanthophyll, violaxanthin, crocetin, astaxanthin, capsanthin. 17. Composition according to one of claims 2, 4, 6 to 16, characterized in that the amino acid (s) is selected from L-arginine and its acid addition salts, glycine, L-glutamine and its amides, L-methionine ). 18. Composition according to one of claims 3, 4, 6 to 17, characterized in that the or the polysaccharides or amylose, pustulan, dextran, amylopectin, cellulose, arabanes, fructans, glucans, such as ß-glucan, mannans, glycogen Chitin Pectins are selected. 19. The composition of claim 1, which contains papain, bromelain, lycopene, vitamin E acetate, vitamin A acetate and sodium selenite as active ingredients. 20. The composition of claim 5, which contains papain, bromelain, lycopene, vitamin E acetate, β-carotene, grape seed flavonoids and sodium selenite as active ingredients. 21. The composition of claim 5, which contains papain, bromelain, vitamin E acetate, a rutin-containing buckwheat extract, quercetin-containing onion powder and L-arginine as active ingredients. 22. The composition of claim 6, which contains papain, bromelain, β-carotene, citrus flavonoids, β-glucan and L-arginine as active ingredients. 23. A composition according to any one of claims 19 to 22, containing: trypsin or chymotrypsin or pepsin; Trypsin + chymotrypsin; Trypsin + chymotrypsin + pepsin; Chymotrypsin + pepsin; Trypsin + pepsin. 24. Food for nutritional supplements, in particular the supplementary balanced diet, to strengthen the immune defense or the body's defenses, to treat inflammatory and inflammatory rheumatic diseases, to regulate the immune system in physical and / or psychological stressful situations, to strengthen the immune system , during and / or after a tumor-destroying treatment or for reducing the risk of tumor recurrences and secondary malignancies, which contains a composition according to one of claims 1 to 23 or consists of such a composition. 25. Medicament, which contains a composition according to one of claims 1 to 23 or consists of such a composition, for strengthening the immune defense or the body's defenses, for the treatment of inflammatory and inflammatory rheumatic diseases, for the regulation of the immune system in physical and / or psychological stressful situations, to strengthen the immune system before, during and / or after tumor-destroying treatment or to reduce the risk of tumor recurrences and secondary malignancies. 26. Use of a composition according to any one of claims 1 to 23 for nutritional supplements, dietary treatment, in particular for the supplementary balanced diet, for regulating the immune system in physical and / or psychological stressful situations, for strengthening the immune defense or the body's own defenses Treatment of inflammatory and inflammatory rheumatic diseases, to strengthen the immune system before, during and / or after a tumor-destroying the treatment or to reduce the risk of tumor recurrences and secondary malignancies. 27. Use of a composition according to any one of claims 1 to 23 for the manufacture of the medicament according to claim 25.