DE10320983A1 - Synergistic cholesterol lowering composition, useful as medicament or food or feed additive, comprising dietary fiber component and ahypocholesterolemic agent, e.g. statin - Google Patents

Abstract

A cholesterol lowering composition (A) comprises at least one dietary fiber component (I) and at least one hypocholesterolemic agent (II), provided that either: (i) (II) is other than an aryl-substituted propanolamine derivative or 1,4-benzothiepin-1,1-dioxide derivative; or (ii) the daily dose of (I) is 1-50 g. A cholesterol lowering composition (A) comprises at least one dietary fiber component (I) and at least one hypocholesterolemic agent (II), provided that either: (i) (II) is other than an aryl-substituted propanolamine derivative or 1,4-benzothiepin-1,1-dioxide derivative; or (ii) the daily dose of (I) is 1-50 g. Independent claims are included for: (a) a cholesterol lowering combination preparation comprising (I) and (II) in separate dosage forms (where proviso (i) or (ii) applies); (b) the preparation of (A) by mixing (I) and (II); ACTIVITY : Antilipemic; antiarteriosclerotic. Hamsters fed a diet enriched with 0.35% cholesterol were treated for 28 days with 2.5% carob fiber (Ia) and/or 1.5 mg % simvastatin (IIa) (both added to feed). The final cholesterol levels in blood serum were 7.65 mM in untreated controls, 7.17 mM (6% reduction) after treatment with (Ia) alone, 6.50 mM (15% reduction) after treatment with (IIa) alone and 5.73 mM (25% reduction, compared with a predicted value of 19%) after treatment with a combination of (Ia) and (IIa). MECHANISM OF ACTION : None given in the source material.

Description

The The invention relates to fiber cholesterol-lowering agents, especially carob fiber, and at least one cholesterol-lowering Active ingredient, especially guglipid and soy protein. Furthermore concerns the invention a process for the preparation of such agents as well their use.

In the context of an unbalanced diet, an excessive content of blood lipid values, in particular blood cholesterol values, is evident in broad sections of the population. A cholesterol level above 200 mg / dl, especially LDL cholesterol levels above 130 mg / dl, is seen as one of the main risk factors for cardiovascular diseases. Therefore, therapeutic treatment is urgently needed in the case of significantly elevated cholesterol levels, especially LDL cholesterol. To this end, a number of approaches have been described so far. In addition to the mostly poorly effective change in lifestyle and diet, a number of special active ingredients have been developed that intervene in different ways in the absorption and metabolism of cholesterol. These include pharmacologically active substances such as statins (among others US 4,231,938 ; US 4,444,784 ; US 4,346,227 ), Inhibitors of bile acid absorption (among others US 5,998,400 ; US 6,277,831 ; US 6,221,897 ) or bile acid sequestrants (among others US 4,027,009 ). All of these active ingredients must be taken under medical prescription and control.

The active ingredients can also include cholesterol-lowering agents isolated from plant sources. The cholesterol-lowering effect of a group of plant sterols, in particular phytosterols, phytostanols and the esters of the compound classes mentioned (inter alia WO 96/38047, WO 99/56558, US 6,087,353 ) to call. However, the latter in particular are not suitable for consumption for all population groups (e.g. exclusion for pregnant women or small children) and are often restricted in their use. Other natural cholesterol-lowering agents also include extracts from other plant sources, such as. B. artichoke extracts, tocotrienol-rich extracts, garlic or guglipid extracts such as those found in the scriptures EP-A-1 238 590 or IN-A-166998 are mentioned. Products containing soy protein also show cholesterol-lowering properties (Anderson JW, Johnstone BM, Cook-Newell ME, Metaanalysis of the effects of soy protein intake on serum lipids, NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (5), 276-82).

Stand against it Food components that have been shown several times adequate intake significantly increases the risk of cardiovascular disease, especially by lowering elevated cholesterol levels can. For fiber as typical food components, it is generally known that high dietary fiber compared to one Low fiber diet positive with a lower risk of cardiovascular disease (Jacobs et al. 1998; Am J Clin Nutr. 68: 248-257; Wolk et al. 1999; JAMA 2281: 1998-2004). In addition to whole grain cereals such as wheat, oats, barley, rye, but also Cereal bran such as oat bran, rice bran, wheat bran, soy bran etc. that are generally high in fiber can also use other fiber a positive contribution to reducing cardiovascular risk and increased Achieve cholesterol levels. So show a number of water soluble Dietary fiber such as β-glucan (from oats or barley), psyllium, pectin or guar gum a lowering Effect on blood cholesterol levels (Brown et al. 1999; Am. J. Clin. Nutr. 69: 30-42).

There are also water-insoluble carob fibers as food components, preferably those produced by a process according to EP-A-0 616780 , are known to significantly lower serum cholesterol levels, especially LDL cholesterol (Zunft et al. 2001; Adv. In Ther. 18: 230-36). The HDL value remains constant, so that the important LDL / HDL ratio shifts towards "good cholesterol" and thus the risk of arteriosclerosis decreases.

The achievable effects lie with the food components well below those achieved with therapeutic agents become, and thus much lower than desirable. Even if one with Dietary fiber, especially enriched with carob fiber Diet with it can help control cholesterol levels, in many cases, especially with very high cholesterol levels (total cholesterol> 300 mg / dl), for sustainable Lowering is not sufficient.

A synergistic, cholesterol-lowering interaction between food components, especially fiber such as carob fiber, and active ingredients is not known. Within the group of food components is even an antagonistic effect for soluble ones, for example Dietary fiber from locust bean gum with water-insoluble Fibers of the carob pulp have been described (Peres-Olleros et al. 1999; J. Sci. Food Agric. 79, 173-178).

The purely pharmacological cholesterol lowerers have the disadvantage that to achieve Thera In some cases, significant concentrations have to be used. Undesirable, sometimes life-threatening side effects can occur, even in combination with other therapeutic agents. Combination therapies to increase the effectiveness with various cholesterol-lowering agents or other therapeutic agents such as B. for cardiovascular diseases are not always usable due to various dangerous contraindications. So show z. B. combinations of fibrates with statins are an increased risk of myopathy syndromes, which could even be fatal in the case of combinations of cerivastatin with gemfibrozil.

Of others are saturation effects Known which cause increased intake of the active ingredient only minor additional Reductions in cholesterol levels can be achieved. Another The disadvantage is the high costs associated with long-term therapy mostly very expensive pharmacological cholesterol lowering occur.

at the cholesterol-lowering agents isolated from plant sources (e.g. Phytosterols) there are quantity limits to undesirable side effects to avoid.

In WO 03/018024 describes combination preparations made from a fiber and 1,4-benzothiepin-1,1-dioxide derivatives and in WO 03/018059 combination preparations from a fiber and aryl-substituted propanolamine derivatives.

It there is therefore still a need for cholesterol-lowering Means that the same or even improved effectiveness Reduce administered amounts of the respective active ingredient and thus the possible side effects and costs, in particular of long-term therapies.

This Task is solved by cholesterol-lowering agents from fiber, in particular Carob fiber, and at least one cholesterol-lowering active ingredient.

Under Dietary fiber in the sense of the invention become components of the plant cells and / or isolated natural or understand carbohydrates obtained through technological processes, those that cannot be absorbed by the human enzyme system in the small intestine Components are dismantled. But you can partially or completely by of the colon flora are fermented. The fiber can for example can be selected from one or more of the following substances: Whole grain cereals (wheat, oats, barley, rye), oat bran (β-glucan), Rice bran, corn bran, barley, psyllium husk (psyllium), guar, carob seeds, Tragacanth, pectin, inulin, non-digestible oligosaccharides, carob pulp, linseed, Soybean fiber, soy bran, dextrins, arabinoxylans, arabinogalactans.

Preferred fibers in the sense of the invention are locust bean fibers, which are characterized by a high content of insoluble fibers but also polyphenols. The total fiber content of the locust bean fiber, determined according to AOAC method 985.29, is at least 30% by weight, preferably at least 60% by weight, but particularly preferably at least 80% by weight (in each case based on the dry matter). Their water-insoluble fiber content, determined according to AOAC method 991.42, is at least 25% by weight, preferably at least 50% by weight, but particularly preferably at least 70% by weight (in each case based on the dry matter). The fiber is produced in such a way that the pulp freed from the carob seeds is separated from the water-soluble carob components in a continuous extraction process and the residue obtained is dried, ground and optionally sieved, particle sizes of <1000 μm, preferably <500 μm and particularly preferably of <200 μm can be obtained. The method according to is particularly preferred EP-A-0 616 780 , The preparations obtained in this way have a pronounced hypocholesterolemic effect and can be used to fortify foods.

Under cholesterol-lowering active ingredients in the sense of the invention are understood as active ingredients that have an elevated cholesterol level (> 200 mg / dl), in particular LDL cholesterol levels> 130 mg / dl. These are characterized by the fact that they specifically determine Affect metabolic processes and thereby secondary to one Lowering LDL cholesterol and total cholesterol (usually between 10-55 %) to lead.

The active ingredients in the context of the invention include cholesterol-lowering substances from the group of statins, bile acid absorption inhibitors and bile acid sequestrants, cholesterol absorption inhibitors, fibrates, nicotinic acid derivatives, but also the group of phytosterols and vegetable stanols and cholesterol-lowering plant extracts, e.g. B. from artichokes or guglipid, as well as soy protein-containing pro -products.

Compounds such as lovastatin [s. Formula 1 below] (e.g. US-A-4,231,938 ), Paravastatin (e.g. US-A-4,346,227 ), Simvastatin [s. Formula 2 below] (e.g. US-A 4,444,784 ), Fluvastatin (e.g. US-A-5,354,772 ), Atorvastatin (e.g. US-A-5,273,995 ) or cerivaststatin (e.g. US-A-5,177,080 ) understood that act specifically by inhibiting cholesterol synthesis (HMG CoA reductase inhibitors) in the liver. These active substances have been described several times and are used to lower cholesterol as medicines and for therapy (e.g. US-A-6,180,660 ) widely used.

Formel 3: Benzothiepin-Derivate (mit R = C₆H₄NHZR₃; R¹,R⁴,R⁵ = Me, Et, Pr, Bu; R² = H, OH, NH₂, Amino(alkyl); R³ = Zuckerrest; Z = -(C=O)_n-(C₀-C₁₆)-Alkyl-, -(C=O)_n-(C₀-C₁₆)-Alkyl-NH-, -(C=O)_n-(C₀-C₁₆)-Alkyl-O-, -(C=O)_n-(C₀-C₁₆)-Alkyl-(C=O)_m oder eine kovalente Bindung; n = 0 oder 1; m = 0 oder 1, sowie deren Salze)

Formel 4: Benzothiazepin-Derivate (mit R¹ = Me, Et, Pr, Bu; R² = H, OH; R³ = Zuckerrest; Z = -(C=O)_n-(C₀-C₁₆)-Alkyl-, -(C=O)_n-(C₀-C₁₆)-Alkyl-NH-, -(C=O)_n-(C₀-C₁₆)-Alkyl-O-, -(C=O)_n-(C₀-C₁₆)-Alkyl-(C=O)_m oder eine kovalente Bindung; n = 0 oder 1; m = 0 oder 1, sowie deren Salze)Inhibitors of bile acid absorption in the sense of the invention are understood to mean substances which prevent the reuptake of bile acids in the intestine / ileum via a process mediated by a receptor. These are in particular benzothiazepine derivatives ( US 5,998,400 . US 6,277,831 ), Benzothiepin-1,1-dioxide derivatives ( US 6,221,897 , WO 97/33882), in particular compounds according to formulas 3 and 4, which specifically block the absorption of bile acid in the intestine, in particular in the ileum.

Formula 3: Benzothiepin derivatives (with R = C ₆ H ₄ NHZR ₃ ; R ¹ , R ⁴ , R ⁵ = Me, Et, Pr, Bu; R ² = H, OH, NH ₂ , amino (alkyl); R ³ = sugar residue; Z = - (C = O) _n - (C ₀ -C ₁₆ ) -alkyl-, - (C = O) _n - (C ₀ -C ₁₆ ) -alkyl-NH-, - (C = O) _n - (C ₀ -C ₁₆ ) alkyl-O-, - (C = O) _n - (C ₀ -C ₁₆ ) alkyl- (C = O) _m or a covalent bond; n = 0 or 1; m = 0 or 1, and their salts)

Formula 4: Benzothiazepine derivatives (with R ¹ = Me, Et, Pr, Bu; R ² = H, OH; R ³ = sugar residue; Z = - (C = O) _n - (C ₀ -C ₁₆ ) alkyl -, - (C = O) _n - (C ₀ -C ₁₆ ) alkyl-NH-, - (C = O) _n - (C ₀ -C ₁₆ ) alkyl-O-, - (C = O) _n - (C ₀ -C ₁₆ ) alkyl- (C = O) _m or a covalent bond; n = 0 or 1; m = 0 or 1, and their salts)

Cholesterol absorption inhibitors are active ingredients that mediate the receptor mediated transport of Inhibit cholesterol and thus cholesterol excretion increase, which ultimately leads to a moderate decrease in serum cholesterol levels. To counting especially hydroxy-substituted azetidinone cholesterol absorption inhibitors from the group 1- (4-fluorophenyl) -3 (R) - [3 (S) - (4-fluorophenyl) -3-hydroxypropyl)] - 4 (S) -4-hydroxyphenyl) -2-azetidinone) and 1- (4-fluorophenyl) -3 (R) - [3 (R) - (4-fluorophenyl) -3-hydroxypropyl)] - 4 (S) -4-hydroxyphenyl) -2-azetidinone) and their pharmacologically active salts or substituted β-lactam cholesterol absorption inhibitors (e.g. WO-A-95/35277, WO-A-02/058733, WO-A-02/50060).

to Group of fibrates belong u. a. Clofibrate, etophylline clofibrate, bezafibrate, ciprofibrate, clinofibrate, binifibrate, Lifibrol, fenofibrate, gemfibrozil or etofibrate. Depending on the clinical picture fibrates have a moderate lowering effect on LDL cholesterol, with a slight improvement in HDL cholesterol levels. Serum triglycerides become stronger through fibrates affected.

nicotinic acid derivatives are natural within the meaning of the invention or synthetically produced nicotinic acid, its esters or synthetic Derivatives such as B. niceritrol, nicofuranose, β-pyridylcarbinol or acipimox. This Substance group has a moderate effect on total and LDL cholesterol, with improved HDL cholesterol levels at the same time.

Under Phytosterols in the sense of the invention are 4-demethylsterols, 4-monomethylsterols and 4,4-dimethylsterols and the respective esters and vegetable Extracts, mixtures and foods rich in phytosterols understood. These include β-sitosterol, Campesterol, stigmatosterol, brassicasterol, desmosterol, chalinosterol, Poriferasterol, Clionasterol and all their natural or synthetic or isomeric derivatives. Vegetable stanols are hydrogenated Plant sterols understood such. B. Campestanol, Sitostanol and the respective esters as well as vegetable extracts, mixtures and Food rich in vegetable stanols.

Further herbal extracts with a cholesterol-lowering effect include u. a. Artichoke extracts and extracts from garlic and guglipid with on. They have long been used as natural remedies and show moderate effectiveness on total and LDL cholesterol levels.

Guglipid (CAS 39025-24-6) in the sense of the invention is the plant exudate from Commiphora mukul. (also Commiphora wightii or Balsamodendron mukul), a tree-like plant from the Burseraceae family. Guglipid in the sense of the invention is also the "Guggulu", "Guggul", "Arka Guggalu" or "Gum Guggul" used in arjuvedic medicine. Furthermore, guglipids in the sense of the invention are the extracts obtained from or from the plants of the Burseraceae family Isolates or pure substances obtained in the sense of the invention are also the guggulsterins and their isomers such as Z-guggulsterin (CAS 85769-67-1), guggulsterin I (CAS 39025-25-7), guggulsterin II (CAS 39025-26-8), Guggulsterin III (CAS 39025-27-9), Guggulsterin IV (CAS 20281-70-3), Guggulsterin V (CAS 6120-71-4), Guggulsterin VI (CAS 61391-01-3) , 16-Epiguggulsterol III (CAS 84709-26-2), E-Guggulsterin, M-Guggulsterin, Dihydro-Guggulsterin-M, Gugulsterin-Y and Guggulsterone Furthermore, for the purposes of the invention, guglipids are all plant sterols found in the plants of the Burseraceae family and stanols, in particular sitosterol, stigmasterol, cholesterol, campesterol and α-spinasterol iters are guglipids in the sense of the invention pharmaceutical products which were produced from the plant exudate or the pure chemical compounds, such as, for example, “gugulipid” from Legere Pharmaceuticals or dietary supplements or food additives such as “CholestGar” from Planetary Formulas.

Under Products containing soy protein in the sense of the invention become food or understood food ingredients that consist of whole soybeans or were made from such, but also those that were processed Contain soy protein products. These include in particular soy protein isolates, Soy protein concentrates, soy flour, textured soy proteins (TSP) or textured plant proteins (TVP). In addition to the protein content can these foods and food ingredients are other naturally occurring Contain soy components such as isoflavones, fiber and saponins.

The agents according to the invention contain at least in addition to the fiber, in particular the carob fiber one or more active ingredient (s). In addition, the cholesterol-lowering agents common additives like solvents, fillers, excipients like methyl cellulose, sweetening carbohydrates and other sweeteners, Flavors, antioxidants, etc. included. The combination of fiber, especially carob fiber, and active ingredients can also be in shape can be administered by two different dosage forms. there offer themselves for the fiber, especially the carob fiber, common food applications such as baked goods, cereals, snack or fruit bars or powdered drinks on. About that is also the direct addition of fiber in food own production as well as use in typical food supplements Form (including tablets, coated tablets, capsules, sachets, granules, bars etc.) possible while the active ingredients are administered in a more typical drug manner (including tablets, coated tablets, capsules, sachets, granules, etc.).

The agents according to the invention contain the active ingredients in amounts that are with 2 to 3 times daily administration are necessary to achieve the therapeutic effect. The Carob fiber component is in the agents according to the invention also contained in concentrations that markedly lower cholesterol cause. The daily dose of carob fiber can be in the range from 1-50 g, usually from 1-25 g, preferably from 5 to 15 g and particularly preferably 5-10 g. It is used in these quantities in combination with the daily ones Doses of the active ingredients are used if a particularly extensive one Reduction in cholesterol is sought. For the so far for single use necessary concentrations of active substances can the use concentrations can be reduced by up to 50–90% due to synergies. Possibly. existing additives can expedient in concentrations from 1-90 % By weight, in particular from 10-60 % By weight (based on the particular preparation form) are added.

to Production of the agents according to the invention moves it’s best to get the amount of fiber you want, in particular carob fiber, and the active ingredient mixes with one another, spray dried, from solvent freed, agglomerated and / or instantized. Furthermore, everyone can common Food technology, but also Gallic manufacturing processes such as pressing, kneading or coating.

at co-administration according to the present invention found that the combined intake of fiber, in particular Carob fiber, and cholesterol-lowering active ingredients into one significantly stronger Lowering cholesterol results in the sum of the effects when administering the individual components. The surprising thing is that the additional Add fiber, especially carob fiber, to the Active substances the activity does not degrade active substances through non-specific interference, but that the observed effects are clearly above the effects achievable with single administration of both substances go out.

The agents according to the invention thus allow a therapeutically often desirable, stronger lowering of cholesterol levels than before or effects in comparable height as before, but with lower amounts of active ingredient. They represent a major advance in drug therapy hypercholesterolemia or hyperlipidemia represents.

The agents according to the invention are expediently used in a suitable preparation which is tailored to the most effective quantitative ratios. For this come z. B. powder or tablet preparations for dissolution, but also chewable tablets in question. These preparations can also other ingredients (additives) to improve the dissolution such as soluble carriers, tablet disintegrants such. B. starch, cellulose, bentonite, pectin or peroxides and carbonates in combination with organic acids and in general colorants, sweeteners such as sucrose, glucose, fructose and other carbohydrates, sugar alcohols such as. As sorbitol, xylitol, maltitol and isomalt or sweeteners such as. B. acesulfame-K, Contain cyclamate, saccharin, sucralose or aspartame and in particular flavorings to improve acceptance.

The agents according to the invention can also be separated in the form of a pharmaceutical preparation of the Active ingredient and one of the fiber, in particular the carob fiber, administer containing food or dietary supplement. For the Active ingredient come the usual Pharmaceutical dosage forms such as tablets, capsules, solutions for Intake as drops or to be dissolved powder preparation or granules in question. Suitable for this combination therapy as a fiber-containing, in particular carob fiber-containing Basically food any food in which the fiber is incorporated can, with limits arising from the properties of the food component as derived from the intended use. Particularly suitable would be accordingly Cereal-based foods such as baked goods, cereals, snack foods and fruit bars, desserts, special diet preparations such as drinks and especially powder drinks based on milk, fruit concentrates or powders, carbohydrates or sugar alcohols. When it comes to phytosterols and plant stanols about that also fatty foods in question such as B. vegetable spread fats, Dressings and dairy products.

The agents according to the invention can still be used as an ingredient in animal nutrition or as animal feed.

in the The invention is explained below using examples.

example 1

Determination of hypocholesterolemic Effect of carob fiber and statins in vivo

The Hamster is considered a suitable animal model to the present Disclose invention even if the metabolic processes in the hamster and differentiate people easily. However, both show here Combination of tested substances on their own in humans a lowering effect on serum cholesterol levels, in particular on the LDL cholesterol. The effect of a combined dose of Carob fiber and a statin, here simvastatin, in this Model should therefore draw conclusions too for the people give.

Male Syrian hamsters (100–120 g at the start of the study) received food enriched with 0.35 cholesterol. The test substances carob fiber, produced according to the method EP-A-0 616 780 , and the statin simvastatin were mixed into the feed individually or in combination. The hamsters were divided into groups of 9 animals and treated with the test substances over a period of 28 days. After anesthesia, blood was obtained for the determination of the serum cholesterol values. The serum cholesterol levels were determined after obtaining the plasma from the whole blood using a commercially available enzyme test kit. The total cholesterol contents of the test groups determined in this way were compared to the results of a control group which received no test substances. The results were as follows: Results:

Example 2

Determination of hypocholesterolemic Effect of carob fiber and phytosterols in vivo

This experiment was carried out analogously to Example 1. Instead of simvastatin, margarine was mixed with phytosterols into the hamster's feed. The final concentration of phytosterols in the feed was 0.5%. Results:

The possible combinations of the agents according to the invention are illustrated by the following combination preparations: Example 3 Powdered preparation (for one serving size) simvastatin 5 mg Carob fiber 3 g Xanthan (stabilizer) 150 mg vanillin 15 mg

Suspend the preparation in 150 ml of lukewarm milk and stir. Example 4 Chewable tablet Vegapure ^® 50 TP (phytosterol ester, Cognis Nutrition & Health, Germany) 400 mg Carob fiber 2 g sorbitol 1.1 g magnesium stearate 15 mg Acesulfame-K 12 mg aspartame 12 mg chocolate flavor qs

The Chewable tablets are more common Wise mixed and pressed.

Claims (22)

Cholesterol-lowering agent containing at least a fiber and at least one cholesterol-lowering active ingredient, except a combination of a) a fiber and b) one aryl-substituted propanolamine derivative or 1,4-benzothiepin-1,1-dioxide derivative. Cholesterol-lowering agent containing at least fiber in a daily dose of 1-50 g and at least one cholesterol-lowering active ingredient. Agent according to claim 1 or 2, characterized in that the fiber selected is made from one or more of the following substances: whole grain cereals, Oat bran, β-glucan, Rice bran, corn bran, barley, psyllium husk, guar, Carob seeds, tragacanth, pectin, inulin, non-digestible oligosaccharides, Carob pulp or one made from carob pulp product obtained, linseed, soy fiber, soy bran, dextrins, Arabinoxylans and arabinogalactans. Agent according to claim 3, characterized in that the carob pulp fiber or one made from carob pulp won product is. Agent according to claim 4, characterized in that the fiber is carob fiber. Agent according to claim 5, characterized in that the fiber is insoluble in water is. Agent according to one of claims 1 to 6, characterized in that that the active ingredient is selected is made up of one or more of the following substances: statins, Inhibitors of bile acid absorption, Gallensäurensequestrantien, Fibrates, nicotinic acid derivatives, Phytosterols, vegetable stanols, cholesterol-lowering vegetable Extrake, guglipid and soy protein products. Cholesterol-lowering combination preparation, containing at least one fiber and at least one cholesterol-lowering Active substance, with the exception of an aryl-substituted propanolamine derivative or 1,4-benzothiepin-1,1-dioxide derivative, in separate dosage forms. Cholesterol-lowering combination preparation, containing at least one fiber in a daily dose of 1-50 g and at least one cholesterol-lowering active ingredient, in separate dosage forms. Combined cholesterol-lowering preparation after Claim 8 or 9, characterized in that the fiber is a food. Combined cholesterol-lowering preparation after Claim 8, 9 or 10, characterized in that the cholesterol-lowering Active ingredient is a food or medicine. Process for the preparation of an agent according to a of claims 1 to 7, characterized in that you have at least one fiber and mixed together at least one cholesterol-lowering active ingredient. Use of an agent according to any one of claims 1 to 7 for the manufacture of a medicament. Use according to claim 13 for the production of a cholesterol lowering drug. Use according to claim 13 for the production of a Medicament for the prophylaxis of hypercholesterolemia, hyperlipidemia or Arteriosclerosis. Use of an agent according to any one of claims 1 to 7 for the production of a food or a food ingredient. Use according to claim 16 for the manufacture of a cholesterol-lowering food or a food ingredient. Use of a combination preparation according to claim 8 or 9 for the manufacture of a medicament. Use according to claim 18 for the production of a cholesterol lowering drug. Use according to claim 18 for the production of a Medicament for the prophylaxis of hypercholesterolemia, hyperlipidemia or Arteriosclerosis. Use of an agent according to any one of claims 1 to 7 in animal nutrition. Use of an agent according to any one of claims 1 to 7 for the production of a feed.