Pharmaceutical Preparations

Abstract

Pharmaceutical preparations are proposed, comprising bitter-masking acting substances for reducing and/or inhibiting gastric acid secretion induced by food constituents.

Claims

1.-15. (canceled)

16. A method for reducing and/or inhibiting secretion of gastric acid induced by food constituents, comprising: administering a gastric acid-inhibiting substance selected from the group consisting of homoeriodictyol and/or eriodictyol to a human who has previously consumed a gastric acid-stimulating component selected from the group consisting of caffeine, theobromine and mixtures thereof and wherein the gastric acid-inhibiting substance is administered prior to gastric acid stimulation in the human by the gastric acid-stimulating component and which is in an amount which inhibits the gastric acid-stimulating effect of the gastric acid-stimulating component in the person.

17. The method of claim 16, wherein the gastric acid-inhibiting substance is administered in amounts of from 0.1 mg/kg to 1,000 mg/kg.

18. The method of claim 16, wherein the gastric acid-inhibiting substance is administered in amounts of from 0.1 mg/kg to 500 mg/kg.

19. The method of claim 16, wherein the gastric acid-inhibiting substance is administered in amounts of from 0.1 mg/kg to 100 mg/kg.

20. The method of claim 16, wherein the gastric acid-inhibiting substance is administered in an orally consumable preparation selected from the group consisting of capsules, tablets, sugar-coated pills, granules, pellets, mixtures of solids, emulsions, powders, and pastes.

21. The method of claim 16, wherein the gastric acid-stimulating component is caffeine.

22. The method of claim 16, wherein the gastric acid-stimulating component is theobromine.

23. The method of claim 16, wherein the gastric acid-inhibiting substance is administered in an orally consumable preparation which is in the form which causes delayed release.

24. The method of claim 16, wherein the gastric acid-stimulating component is present in a preparation selected from the group consisting of bakery products, confectionery, alcoholic or non-alcoholic drinks, meat products, eggs or egg products, cereal products, milk products, products made from soy protein or other soybean fractions, fruit preparations, vegetable preparations, snack foods, products based on fat and oil or emulsions of the same, other ready meals and soups, spices, spice mixtures and seasonings.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention will be described in greater detail with reference to the accompanying drawings, in which

[0019] FIG. 1 illustrates a graph of proton secretion on exposure to caffeine or caffeine/enterolactone, and

[0020] FIG. 2 illustrates a graph of proton secretion on exposure to enterolactone.

BITTER-MASKING SUBSTANCES (COMPONENT A)

[0021] The bitter-masking substances which can form component (a) are selected from the group formed by: [0022] hydroxyflavanones, particularly eriodictyol, eriodictyol-7-methyl ether, homoeriodictyol, and sodium, potassium, calcium, magnesium or zinc salts thereof, especially those which are described in the European patent application EP 1258200 A2; [0023] hydroxybenzamides, particularly those which are described in the international patent application WO 2006 024587 A2; [0024] hydroxyphenylalkanediones, particularly gingerdione-[2] and gingerdione-[3], and especially those which are described in the international patent application WO 2007 003527 A2; [0025] gamma-aminobutyric acid, particularly those which are described in the international patent application WO 2005 096841 A1; [0026] 4-hydroxydihydrochalcones, particularly phloretin and those which are disclosed in the international patent application WO 2007 107596 A1; [0027] vanillyl lignans, particularly matairesinol, lariciresinol, hydroxymatairesinol which are disclosed, for example, in the international patent application WO 2012 146,584, and particularly also [0028] enterolactone.

[0029] Bitter-Masking Food Constituents Inducing Secretion of Gastric Acid (Component b)

[0030] These substances comprising the component (b) are selected from the group formed by: [0031] xanthines, particularly caffeine, theobromine and theophylline; [0032] fruit acids, particularly tartaric acid, racemic acid, malic acid and succinic acid; [0033] phenolic glycosides, particularly salicin and arbutin; [0034] flavanone glycosides, particularly neohesperedin, eriocitrin, neoeriocitrin, narirutin and naringin; [0035] dihydrochalcone glycosides, particularly phloridzin, trilobatin; [0036] hydrolyzable tannins, particularly gallic or ellagic esters or carbohydrates, e.g. pentagalloyl glucose; [0037] non-hydrolyzable tannins, particularly galloylated catechins or epicatechins and oligomers thereof, e.g. proanthyocyanidins or procyanidins, thearubigins, flavones and glycosides thereof, particularly quercetin, quercitrin, rutin, taxifolin, myricetin, myrictrin; [0038] terpenoid bitter substances, particualrly limonin, nomilin, lupolone and humolone; [0039] triterpene glycosides, particualrly steviosides, rubusoside, stevioside, rebaudioside A, rebaudioside C, glycyrrhizin (glycyrrhizic acid) and glycyrrhetic acid; and [0040] iridoid bitter substances such as oleuropein
and mixtures thereof.

Preferred Embodiments

[0041] The highest reduction or complete inhibition of the induced gastric acid secretion was observed in preparations which comprised caffeine and/or theobromine as component (b) and to which was added one of the following substances of component (a), namely homoeriodictyol (1), eriodictyol (2), matairesinol (3), lariciresinol (4) and/or enterolactone (5). Corresponding preparations are therefore particularly preferred.

[0042] The bitter-masking substances which can form component (a) are selected from the group formed by:

[0043] The preferred compounds are shown again in the following Figure:

##STR00001##

[0044] In principle, the therapeutic preparations may comprise both the substances which form component (a) and (b), in each case in amounts of approximately 0.1 mg/kg (corresponding to 0.1 ppm) to approximately 1% by weight. However, the substances are preferably present in each case in amounts of approximately 0.5 to approximately 1000 mg/kg (corresponding to approximately 0.5 to approximately 1000 ppm), preferably of approximately 1 to approximately 500 mg/kg, more preferably of approximately 3 to approximately 300 mg/kg, particularly preferably of approximately 5 to approximately 200 mg/kg and most preferably of approximately 10 to 100 mg/kg.

[0045] The preparations according to the invention may comprise the substances which form components (a) and (b) in the weight ratio of approximately 1:100 to approximately 1:1, preferably 1:90 to approximately 1:2 and particularly of approximately 1:5 to approximately 1:10.

[0046] Oral Preparations

[0047] The present invention further relates to a preparation for oral administration, specifically providing nutrition or enjoyment, comprising as already elucidated in detail above [0048] (a) bitter-masking acting substances and [0049] (b) substances which induce the secretion of gastric acid.

[0050] The preparations providing nutrition or enjoyment (i.e. suitable for consumption) are, in the context of this invention, e.g. bakery products (e.g. bread, dry biscuits, cakes, other baked goods), confectionery (e.g. chocolates, chocolate bar products, other bar products, fruit gums, hard and soft caramels, chewing gum), alcoholic or non-alcoholic drinks (e.g. coffee, tea, wine, wine-based drinks, beer, beverages containing beer, liqueurs, spirits, brandies, fruit-containing carbonated beverages, isotonic drinks, soft drinks, nectars, fruit and vegetable juices, fruit or vegetable juice preparations), instant drinks (e.g. instant cocoa drinks, instant tea drinks, instant coffee drinks), meat products (e.g. ham, fresh or cured sausage, spiced or marinated fresh or cured meat), eggs or egg products (dried egg, egg white, egg yolk), cereal products (e.g. breakfast cereals, muesli bars, precooked instant rice products), dairy products (e.g. milk drinks, ice milk, yogurt, kefir, cream cheese, soft cheese, hard cheese, dried milk powder, whey, butter, buttermilk, partially or fully hydrolyzed milk protein-containing products), products made from soy protein or other soybean fractions (e.g. soy milk and products manufactured therefrom, preparations containing soy lecithin, fermented products such as tofu or tempeh or products manufactured therefrom, soy sauce), fruit preparations (e.g. jams, fruit ice cream, fruit sauces, fruit fillings), vegetable preparations (e.g. ketchup, sauces, dried vegetables, frozen vegetables, precooked vegetables, pickled vegetables, cooked vegetables), snack foods (e.g. baked or fried potato chips or reconstituted potato products, bread dough products, extrudates based on maize or peanut), products based on fat and oil or emulsions of the same (e.g. mayonnaise, remoulade, dressings, seasoning preparations), other ready meals and soups (e.g. dried soups, instant soups, precooked soups), spices, spice mixtures and especially seasonings which are used in the snack food sector.

[0051] The oral preparations in the context of the invention may also serve as semi-finished goods for the preparation of further orally consumable preparations. The preparations in the context of the invention may also be in the form of capsules, tablets (oral and/or gastric disintegrating tablets), sugar-coated pills, granules, pellets, mixtures of solids, dispersions in liquid phases, as emulsions, as powders, as solutions, as pastes or as other swallowable or chewable preparations as food supplements.

[0052] Preference is given here to incorporating one or more of the substances of group (a) in an orally consumable preparation, particularly in the form of preparations which can be swallowed (e.g. drinks, dispersions, emulsions, pastes, capsules which can dissolve in the mouth or stomach, tablets, compressed products, soft caramels, sugar-coated pills, granules, pellets, fruit gums) or in preparations not intended to be swallowed (e.g. chewing gum, hard caramels) releasing sufficient concentrations of substances of group (a) in an effective concentration.

[0053] The substances of group (a) to be used in accordance with the invention in preparations suitable for consumption in accordance with the invention, particularly in the preferred concentrations to be used in accordance with the invention, have no appreciable taste of their own and in particular they have no unpleasant or objectionable flavors at the (preferred or particularly preferred) concentrations employed. The substances of group (a) are each capable alone and/or in mixtures to reduce or to completely block the bitterness of one or more of the substances of group (b).

[0054] The substance(s) of group (a) and also preparations according to the invention comprising the substance(s) of group (a), can be fed orally in time sequence before, during or after oral administration of the substance(s) of group (b) or preparations comprising the substance(s) of group (b).

[0055] Particularly advantageous here is the known fact that the substances of group (a) are regularly capable of partially or completely reducing the bitter (unpleasant) taste of the substances of group (b) and therefore can significantly increase the acceptability of the preparations. This is particularly the case if the substances of group (b) are applied at the same time as the substances of group (a).

[0056] In the case of subsequent oral administration of the substance(s) of group (a), preparation forms are preferred which comprise the substance(s) of group (a) in a form which causes delayed release.

[0057] In an alternative to the simultaneous oral administration, preparations may also be suitable which have one or more of the unpleasant tasting and gastric acid-stimulating substances of group (b) in an effective amount with respect to gastric acid stimulation and simultaneously comprise one or more of the substances of group (a) in an effective amount with respective to gastric acid stimulation.

[0058] In principle, the oral preparations may comprise—be they finished or semi-finished products—both the substances which form component (a) and (b), in each case in amounts of approximately 0.1 mg/kg (corresponding to 0.1 ppm) to approximately 1% by weight. However, the substances are preferably present in each case in amounts of approximately 0.5 to approximately 1000 mg/kg (corresponding to approximately 0.5 to approximately 1000 ppm), preferably of approximately 1 to approximately 500 mg/kg, more preferably of approximately 3 to approximately 300 mg/kg, particularly preferably of approximately 5 to approximately 200 mg/kg and most preferably of approximately 10 to 100 mg/kg.

[0059] The preparations according to the invention may comprise the substances which form components (a) and (b) in the weight ratio of approximately 1:100 to approximately 1:1, preferably 1:90 to approximately 1:2 and particularly of approximately 1:5 to approximately 1:10.

INDUSTRIAL APPLICABILITY

[0060] A preferred method for determining the desired effect of substances of group (a) on decreasing the effect of substances of group (b) consists of measuring the intracellular pH of HGT-1 cell cultures (human gastric tumor cell line) after treatment with the test substances as described in Liszt, K. I.; Walker, J.; Somoza, V. J. Agric Food Chem. 2012, 60, (28), 7022-7030. To date, only the somatostatin receptor (SSTR2) on the cell surface of gastric acid-secreting cells has been described as a target for reducing the secretion; this receptor has also been described in HGT-1 To date, these cells have only ever been brought into contact with potential SSTR2 regulators; the co-administration of bitter agonists and potential antagonists has not been described to date.

[0061] Two further aspects of the present invention relate firstly to a non-therapeutic method for reducing and/or inhibiting secretion of gastric acid induced by food constituents, in which an effective amount of a bitter-masking acting substance is orally administered to a human or animal, and secondly the use of bitter-masking acting substances for reducing and/or inhibiting the secretion of gastric acid induced by food constituents. With regard to the nature of the substances and the amounts used thereof, reference is made to the embodiments above which are fully incorporated here.

EXAMPLES

[0062] Cell model

[0063] Human parietal cells, also known as human gastric tumor cell line (HGT-1), are used as cell model. These were provided by Dr. C. Laboisse (Laboratory of Pathological Anatomy, Nantes, France). The cells were cultured under standard conditions at 37° C., 5% CO.sub.2 in DMEM (Dulbecco's Modified Eagle's Medium) with 4 g/l glucose, 10% FBS, 2% L-glutamine and 1% penicillin/streptomycin. For the measurement of the intracellular proton concentration, the cells are treated with trypsin/EDTA, the viability determined by means of trypan blue staining and 100 000 cells/well seeded in black 96-well plates.

Example 1

[0064] Determination of the intracellular pH of HGT-1 cell cultures in the presence of the substances of group (a) and substances of group (b)

[0065] To measure the intracellular pH, the dye 1,5 -carboxyseminaphthorhodafluoro acetoxymethyl ester (SNARF-1-AM) is used. The cells in the 96-well plates are washed once with Krebs-Hepes buffer (KRHP) and incubated at 37° C. and 5% CO.sub.2 for 30 min with the dye dissolved in KRHP at a concentration of 3 μM. The cells are then washed twice with KRHP and substances of group (b), for example 3 mM caffeine or 0.3 mM theobromine, alone or in combination with substances of group (a), for example, homoeriodictyol (HED) or eriodictyol or matairesinol, lariciresinol or enterolactone, are applied in volumes of 100 μl at various concentrations in phenol red-free DMEM; as additional control experiments, the abovementioned substances of group (a) are tested alone. Homoeriodictyol is dissolved in double-distilled water while eriodictyol, matairesinol, lariciresinol or enterolactone are dissolved in ethanol (EtOH). The final concentration of solvent which is added to the cells is at most 1%. The fluorescent dye is excited at a wavelength of 488 nm and the emission measured at 580 nm and 640 nm. The ratio of the fluorescence values at 580 nm to 640 nm is compared to a calibration curve from which the pH can be determined. For the calibration curve, the cells are treated with a potassium phosphate buffer of different pH values from pH 7.2-8.2 and 2 μM nigericin. Nigericin equilibrates the intracellular and extracellular pH such that the intracellular pH may be defined. The intracellular H.sup.+ concentration is determined from the intracellular pH. The intracellular proton index (IPX) is calculated by log 2 transformation of the ratio of treated cells and untreated cells (control). The results given here are stated as percentage changes compared to untreated control cells (cf. Malte Rubach, R. L., Elisabeth Seebach, Mark M. Somoza, Thomas Hofmann; Somoza, a. V., Mol Nutr Food Res. in press, 2011; Rubach, M.; Lang, R.; Hofmann, T.; Somoza, V., Ann N Y Acad Sci 2008, 1126, 310-4; Rubach, M.; Lang, R.; Skupin, C.; Hofmann, T.; Somoza, V., J Agric Food Chem 2010, 58, 4153-61; Weiss, C.; Rubach, M.; Lang, R.; Seebach, E.; Blumberg, S.; Frank, O.; Hofmann, T.; Somoza, V., J Agric Food Chem 2010, 58, 1976-85; Liszt, K. I.; Walker, J.; Somoza, V., J Agric Food Chem 2012; Walker, J.; Hell, J.; Liszt, K. I.; Dresel, M.; Pignitter, M.; Hofmann, T.; Somoza, V., J Agric Food Chem 2012, 60, 1405-12). The number of replicates specified refers to the technical replicates (tr) or the number or total replicates (n), which results from the number of technical replicates multiplied by the number of biological replicates.

[0066] Given in Table 1A below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM or DMEM with 1% ETOH or 1 mM histamine or 3 mM caffeine with and without 1% EtOH. The data are presented as mean values and mean standard deviations, n=21-37, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00001 TABLE 1A Comparative Example, increase in secretion due to substances of group (b). Test substance T/C [%] SEM Control (DMEM) 0.150 1.00 a EtOH 1% 14.44 2.61 b 1 mM Histamine 27.42 3.17 b 3 mM Caffeine 48.87 3.64 d 3 mM Caffeine + 1% EtOH 44.92 3.51 d

[0067] Given in Table 1B below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM or DMEM with 1% ETOH or 1mM histamine or 0.3 mM theobromine with and without 1% EtOH. The data are presented as mean values and mean standard deviations, n=21-37, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00002 TABLE 1B Comparative Example, increase in secretion due to substances of group (b). Test substance T/C [%] SEM DMEM (control) 0.15 1.00 a 1% EtOH 14.44 2.61 b 1 mM Histamine 27.42 3.17 b, c 0.3 mM Theobromine 17.51 2.65 b 0.3 mM Theobromine + 1% 32.11 2.49 c, d EtOH

[0068] Given in Table 2A below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM (control) or homoeriodictyol (HED) at various concentrations. The data are presented as mean values and mean standard deviations, n=4, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00003 TABLE 2A Influence on the secretion by substances of group (a). Test substance T/C [%] SEM DMEM (control) −1.43 2.01 a 0.003 mM HED −8.04 3.88 a 0.03 mM HED 12.70 4.02 a 0.3 mM HED −3.66 5.24 a

[0069] Given in Table 2B below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM (control) or eriodictyol at various concentrations. The data are presented as mean values and mean standard deviations, n=3-7, tr=6. Statisitics: one-way Anova with post-hoc test according to

[0070] Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00004 TABLE 2B Influence on the secretion by substances of group (a). Test substance T/C [%] SEM Control (DMEM) 0.98  2.30 a 0.03 mM Eriodictyol −10.77 11.16 a 0.3 mM Eriodictyol −11.67  7.25 a

[0071] Given in Table 2C below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with matairesinol at various concentrations. The data are presented as mean values and mean standard deviations, n=8, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00005 TABLE 2C Influence on the secretion by substances of group (a). Test substance T/C [%] SEM DMEM (control) −0.63 1.70 a 0.03 mM Matairesinol −9.40 3.73 a 0.3 mM Matairesinol −31.69 2.95 b

[0072] Given in Table 2D below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM (control) or lariciresinol at various concentrations. The data are presented as mean values and mean standard deviations, n=8, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00006 TABLE 2D Influence on the secretion by substances of group (a). Test substance T/C [%] SEM Control (DMEM) 0.15 1.93 a 0.03 mM Lariciresinol 6.40 4.46 a 0.3 mM Lariciresinol −2.04 2.78 a

[0073] Given in Table 2E below and also FIG. 1 is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by DMEM (control) or enterolactone at various concentrations. The data are presented as mean values and mean standard deviations, n=8, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00007 TABLE 2E Influence on the secretion by substances of group (a). Test substance T/C [%] SEM Control (DMEM) −2.28 1.80 a 0.03 mM Enterolactone −2.76 3.75 a 0.3 mM Enterolactone −27.31 4.43 a

[0074] Given in Table 3A below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with homoeriodictyol (HED) at various concentrations. The data are presented as mean values and mean standard deviations, n=4, tr=6. Statisitics: one-way

[0075] Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00008 TABLE 3A Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 3 mM Caffeine 54.79 5.61 a 3 mM Caffeine + 0.03 mM HED 37.99 6.70 a 3 mM Caffeine + 0.3 mM HED 20.18 5.99 b

[0076] Given in Table 3B below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with eriodictyol at various concentrations. The data are presented as mean values and mean standard deviations, n=4, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00009 TABLE 3B Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 3 mM Caffeine 54.05 4.37 a 3 mM Caffeine + 0.03 mM Eriodictyol 29.69 8.82 a 3 mM Caffeine + 0.3 mM Eriodictyol −33.96 7.55 b

[0077] Given in Table 3C below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with matairesinol at various concentrations. The data are presented as mean values and mean standard deviations, n=4, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00010 TABLE 3C Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 3 mM Caffeine  38.75 2.63 a 3 mM Caffeine + 0.03 mM Matairesinol  14.39 3.55 b 3 mM Caffeine + 0.3 mM Matairesinol −20.43 4.82 c

[0078] Reproduced in Table 3D below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with lariciresinol at various concentrations. The data are presented as mean values and mean standard deviations, n=5, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00011 TABLE 3D Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 3 mM Caffeine 52.41 4.16 a 3 mM Caffeine + 0.03 mM Lariciresinol 46.40 3.98 a 3 mM Caffeine + 0.3 mM Lariciresinol 21.57 3.78 b

[0079] Reproduced in Table 3E below and also FIG. 2 is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 3 mM caffeine or 3 mM caffeine in combination with enterolactone at various concentrations. The data are presented as mean values and mean standard deviations, n=5, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00012 TABLE 3E Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 3 mM Caffeine  34.12 2.86 a 3 mM Caffeine + 0.03 mM Enterolactone  23.41 2.56 a 3 mM Caffeine + 0.3 mM Enterolactone −18.25 3.39 b

[0080] Reproduced in Table 3F below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 0.3 mM theobromine or 0.3 mM theobromine in combination with homoeriodictyol (HED) at various concentrations. The data are presented as mean values and mean standard deviations, n=3, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00013 TABLE 3F Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 0.3 mM Theobromine  20.92 3.37 a 0.3 mM Theobromine + 0.003 mM HED  21.56 2.33 a 0.3 mM Theobromine + 0.03 mM HED  13.79 3.50 a 0.3 mM Theobromine + 0.3 mM HED −16.92 3.27 b

[0081] Reproduced in Table 3G below is the proton secretion in HGT-1 cells after 10 minutes stimulation by 0.3 mM theobromine or 0.3 mM theobromine in combination with eriodictyol at various concentrations. The data are presented as mean values and mean standard deviations, n=3, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00014 TABLE 3G Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 0.3 mM Theobromine  47.64 5.28 a 0.3 mM Theobromine + 0.03 mM Eriodictyol  23.95 4.17 b 0.3 mM Theobromine + 0.3 mM Eriodictyol −42.86 9.73 c

[0082] Reproduced in Table 3H below is the proton secretion in HGT-1 cells after 10 minutes stimulation by 0.3 mM theobromine or 0.3 mM theobromine in combination with matairesinol at various concentrations. The data are presented as mean values and mean standard deviations, n=3, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00015 TABLE 3H Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 0.3 mM Theobromine  34.12 2.86 a 0.3 mM Theobromine + 0.03 mM Matairesinol  23.41 2.56 b 0.3 mM Theobromine + 0.3 mM Matairesinol −18.25 3.39 c

[0083] Reproduced in Table 31 below is the percentage increase of the proton secretion in HGT-1 cells compared to untreated controls after 10 minutes stimulation by 0.3 mM theobromine or 0.3 mM theobromine in combination with lariciresinol at various concentrations. The data are presented as mean values and mean standard deviations, n=3, tr=6. Statisitics: one-way Anova with post-hoc test according to Dunn. Significant differences (p<0.05) are indicated by letters.

TABLE-US-00016 TABLE 3I Decrease in the secretion, triggered by substances of group (b), by substances of group (a) Test substance T/C [%] SEM 0.3 mM Theobromine 30.81 3.44 a 0.3 mM Theobromine + 0.03 31.73 5.80 a mM Lariciresinol 0.3 mM Theobromine + 0.3 17.55 3.67 a mM Lariciresinol (t-test p <0.05)

[0084] As follows from Tables 1A and 1B, the proton secretion in the HGT-1 cells is stimulated by substances of group (b), in this case caffeine or theobromine, which effectively triggers acid secretion into the extracellular space. The substances of group (a) alone lead either to no significant effect (Tables 2A, 2B and 2D) or even to a significant decrease of the constitutive acid secretion (Table 2C). The stimulation of proton secretion by 3 mM caffeine (Tables 3A-3E) or 0.3 mM theobromine (Tables 3F-3I) could be reduced or completely inhibited by additional administration of the substances of group (a), particularly homoeriodictyol, eriodictyol, matairesinol, lariciresinol or enterolactone at a concentration of 0.3 mM.

Application Example 1

[0085] Spray-dried preparation as semi-finished goods for preparing finished goods.

[0086] Drinking water is placed in a container and maltodextrin and gum arabic dissolved therein. The substances of group (a) are then emulsified in the carrier solution using a Turrax. The temperature of the spray solution should not exceed 30° C. The mixture is then spray-dried (nominal temperature at the start: 185-195° C., nominal temperature at the end: 70-75° C.). The spray-dried semi-finished goods comprise ca. 18-22% of the compounds of group (a).

TABLE-US-00017 TABLE 4 Semi-finished goods composition- amounts in % by weight. Preparation A B C D E Drinking water 60.8 60.8 60.8 60.8 60.8 Maltodextrin from wheat 24.3 24.3 24.3 24.3 24.3 Gum arabic  6.1  6.1  6.1  6.1  6.1 Matairesinol  8.8 —  4.4 — — Homoeriodictyol —  8.8  4.4 — — Eriodictyol — — —  8.8 — Enterolactone — — — —  8.8

Application Example 2

Drinkable Iced Tea Preparation

[0087] The compounds of group (a) were each pre-dissolved at 10% in ethanol. Black tea extract was dissolved in water and stirred in a glass beaker together with sugar, a flavoring preparation (peach flavor) and the ethanolic solutions of the compounds of group (a).

TABLE-US-00018 TABLE 5 Iced tea composition-amounts in % by weight. Preparation A B Black tea extract 1.4 1.4 Water 89.5 89.5 Flavoring preparation (peach type) 0.65 0.65 Sugar 7.0 7.0 Citric acid (crystalline) 1.2 1.2 Ascorbic acid 0.2 0.2 Matairesinol in ethanol (10%) 0.05 — Homoeriodictyol in ethanol (10%) — 0.05

Application Example 3

[0088] Gelatine capsules without substances of group (b) for direct consumption after application of substances of group (b).

[0089] The gelatine capsules suitable for direct consumption were prepared according to WO 2004/050069 and had a diameter of 5 mm and the ratio by weight of core material to shell material was 90:10. The capsules opened in the mouth within less than 10 seconds and dissolved completely in less than 50 seconds.

TABLE-US-00019 TABLE 6 Gelatine capsule composition-amounts in % by weight. Ingredients A B C Gelatine shell: Glycerol 2.014 2.014 2.014 Gelatine 240 Bloom 7.91 7.91 7.91 Sucralose 0.065 0.065 0.065 Allura red 0.006 — 0.011 Brilliant blue 0.005 0.011 — Core composition Vegetable oil triglyceride 79.49 68.55 58.55 (coconut oil fraction) Orange flavoring comprising 10.0 — — 1% by weight homoeriodictyol based on the total weight of the flavoring. Peppermint flavoring comprising — 20.0 — 1% by weight matairesinol based on the total weight of the flavoring. Cherry flavoring comprising 1% — — 28.65 by weight enterolactone based on the total weight of the flavoring. Rebaudioside A 98% 0.05 0.05 — 2-Hydroxypropylmenthylcarbonate 0.33 0.20 — 2-Hydroxyethylmenthylcarbonate — 0.20 1.00 (1R,3R,4S) Menthyl-3-carboxylic — 0.55 — acid N-ethylamide (WS-3) (-)-Menthyl lactate (Frescolat ML) — 0.30 — Vanillin 0.07 — 0.10

Application Example 4

[0090] Chewing Gum without Substances of Group (B)

[0091] Parts A to D are mixed and kneaded intensively. The crude mass may be processed, for example in the form of thin strips, to form ready-to-consume chewing gum.

TABLE-US-00020 TABLE 7 Chewing gum composition-amounts in % by weight. Part Preparation A B A Chewing gum base, “Jagum T” company 30.00 30.00 B Sorbitol, powdered 39.00 39.00 Isomale.sup. ® (Palatinit GmbH)  9.50  9.50 Xylitol  2.00  2.00 Mannitol  3.00  3.00 Aspartame.sup. ®  0.10  0.10 Acesulfame.sub. ® K  0.10  0.10 Emulgum.sup. ® (Colloides Naturels, Inc.)  0.30  0.30 C Sorbitol, 70% 14.00 14.00 Glycerol  1.00  1.00 D Mint flavoring comprising 1% matairesinol  1.00 — based on the total weight of the flavoring. Tutti frutti flavoring comprising —  2.00 1% homoeriodictyol based on the total weight of the flavoring.

Application Example 5

Use in a Soluble Cappuccino Drink

[0092] The specified raw materials are mixed. In each case 12.5 g of the prepared instant cappuccino powder are dissolved in 150 ml of hot water.

TABLE-US-00021 TABLE 8 Cappuccino drink composition-amounts in % by weight. Preparation A B Coffee extract, spray-dried 14.0 16.0 Sugar 28.3 25.3 Fat powder 18.2 18.2 Coffee whitener, foaming 30.0 28.0 Hydrocolloids/emulsifiers  1.8  1.8 Lactose  4.7  4.7 Semi-finished product A  3.0 — from application example 1 Semi-finished product B —  6.0 from application example 1

Application Example 6

Tea Drink

[0093] The tea and the semi-finished goods are mixed and packed in tea bags made of filter paper. To use, one tea bag is infused in 100-250 ml of boiling water and left to draw for 2-5 min.

TABLE-US-00022 TABLE 9 Tea drink composition-amounts in % by weight. Preparation A B C Black tea, Ceylon, leaf product 94.00 — — Green tea, China, leaf product — 91.90 — Mate tea, Peru, leaf product — — 95.00 Semi-finished product A  6.0 — from application example 2 Semi-finished product B —  8.0 — from application example 2 Semi-finished product C — —  5.0 from application example 2 Flavor (lemon type) —  0.1 —

Application Example 7

Use in a Bitter Chocolate

[0094] A bitter chocolate was prepared from the following raw materials and subsequently poured into rectangular forms.

TABLE-US-00023 TABLE 10 Chocolate composition-amounts in % by weight. Preparation A B Cocoa mass 55.55 55.55 Cocoa butter 11.70 11.70 Sugar 29.50 29.50 Skimmed milk  3.00  3.00 Lecithin  0.2  0.2 Vanillin  0.035  0.035 10% Matairesinol in ethanol —  0.05 10% Homoeriodictyol in ethanol  0.05 —

Application Example 8

Sugar-Free Hard Caramel

[0095] Palatinit was mixed with water and the mixture melted at 165° C. and subsequently cooled to 115° C. The remaining constituents were added and, after mixing, poured into molds, removed from the molds after solidification and then individually packaged.

TABLE-US-00024 TABLE 11 Caramel composition-amounts in % by weight. Preparation A B C D Palatinat, type M 75.00 74.00 75.50 75.00 Citric acid — 1.0 0.5 — Water 24.88 24.842 23.88 24.844 Yellow coloring — 0.01 — — Red coloring — — 0.01 — Blue coloring 0.01 — — 0.01 Peppermint flavoring 0.1 — — 0.1 Lemon flavoring — 0.1 — — Red fruit flavoring — — 0.1 — Rebaudioside A 98% — 0.040 — 0.040 Hesperetin — 0.001 — 0.001 Phloretin — 0.002 — — Homoeriodictyol 0.010 0.005 — 0.005 Matairesinol — 0.005 — — Eriodictyol — — 0.010 — Enterolactone — — — 0.005