HOMOVANILLIC ACID ESTER FOR REDUCING OR INHIBITING FATTY ACID ABSORPTION IN THE SMALL INTESTINE

Abstract

The present invention particularly relates to new uses of compounds of formula (I) (as described herein) for inhibiting or reducing the absorption of free fatty acids in the small intestine, as well as a new compound of formula (I) as such, aroma compositions and new compositions comprising such a compound of formula (I). Further aspects of the present invention result from the patent claims and the subsequent description including the examples.

Claims

1-11. (canceled)

12. A compound of formula (I): ##STR00056## wherein (i) R.sup.1 and R.sup.2 independently represent a hydrogen atom or an alkyl group with 1-2 carbon atoms, R.sup.3 and R.sup.4 independently represent a hydrogen atom or a linear or branched alkyl group with 1 to 5 carbon atoms, a phenyl group, an alkyl phenyl group, a phenyl alkyl group, a linear or branched alkenyl group with 2 to 4 carbon atoms, an alkenyl phenyl group, or a phenyl alkenyl group, or (ii) R.sup.1 and R.sup.3 form, together with the carbon atoms connecting these, a cyclohexyl ring, which is optionally substituted with a substituent R.sup.5, wherein R.sup.5 is an alkyl group with 1-2 carbon atoms, R.sup.2 represents a hydrogen atom or an alkyl group with 1-2 carbon atoms, R.sup.4 represents a hydrogen atom or a linear or branched alkyl group with 1 to 5 carbon atoms, a phenyl group, an alkyl phenyl group, a phenyl alkyl group, a linear or branched alkenyl group with 2 to 4 carbon atoms, an alkenyl phenyl group, or a phenyl alkenyl group, or a physiologically acceptable salt thereof, wherein the phenolic hydroxyl group in formula (I) is deprotonated.

13. A compound of claim 12, wherein R.sup.1 and R.sup.2 are each a hydrogen atom, R.sup.3 represents a hydrogen atom, a linear or branched alkyl group with 1 to 4 carbon atoms, a phenyl group, an alkyl phenyl group, a phenyl alkyl group, an alkenyl phenyl group, or a phenyl alkenyl group, and R.sup.4 is a hydrogen atom, or a physiologically acceptable salt thereof.

14. A compound of claim 13 selected from the group consisting of: 2-Phenylethyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (1) ##STR00057## [(E)-Cinnamyl]-2-(4-hydroxy-3-methoxy-phenyl)acetate (2) ##STR00058## [(E)-Hex-2-enyl]-2-(4-hydroxy-3-methoxy-phenyl)acetate (5) ##STR00059## [(Z)-Hex-3-enyl]-2-(4-hydroxy-3-methoxy-phenyl)acetate (6) ##STR00060## Heptyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (13) ##STR00061## Ethyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (16) ##STR00062## Propyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (17) ##STR00063## Butyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (18) ##STR00064## Pentyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (19) ##STR00065## Hexyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (20) ##STR00066## 3-Phenylpropyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (21) ##STR00067## 4-Phenylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (22) ##STR00068## or a physiologically acceptable salt thereof.

15. A compound of claim 12, wherein R.sup.1 and R.sup.2 independently represent a hydrogen atom, methyl, or ethyl, R.sup.3 and R.sup.4 independently represent a hydrogen atom or a linear or branched alkyl group with 1 to 5 carbon atoms, or a physiologically acceptable salt thereof.

16. A compound of claim 12 selected from the group consisting of: 1-Ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (3) ##STR00069## 3-Methylbut-2-enyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (4) ##STR00070## Isopropyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (7) ##STR00071## sec-Butyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (8) ##STR00072## Isobutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (9) ##STR00073## Isopentyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (10) ##STR00074## 2-Methylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (11) ##STR00075## 1-Methylpentyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (12) ##STR00076## 1-Methylhexyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (14) ##STR00077## (2-Isopropyl-5-methyl-cyclohexyl)-2-(4-hydroxy-3-methoxy-phenyl)acetate (15) ##STR00078## 2-Ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) ##STR00079## or a physiologically acceptable salt thereof.

17. A compound of claim 12 represented by formula (Ia) ##STR00080## wherein, R.sup.2 is a hydrogen atom, and R.sup.4 is 2-propyl, or a physiologically acceptable salt thereof.

18. A mixture comprising one or more compounds of claim 12 and/or a physiologically acceptable salt thereof.

19. An aroma composition comprising a compound of claim 12, wherein the compound is 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) ##STR00081## or a physiologically salt thereof.

20. A pharmaceutical composition comprising a compound of claim 12, wherein the compound is 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) ##STR00082## or a physiologically salt thereof.

21. The composition of claim 20, further comprising: up to 99.9999 wt. %, relative to the total weight of the composition, of basic materials, excipient, and/or additives; and/or up to 99.9999 wt. %, relative to the total weight of the composition, of water.

22. The composition of claim 20, wherein the total amount of 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate and/or physiologically acceptable salt(s) thereof is sufficient to inhibit or reduce the absorption of free fatty acids in the small intestine.

23. A method for producing the pharmaceutical composition of claim 20 comprising: i) providing 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) and/or physiologically acceptable salt(s) thereof, ii) providing one or more further components of the pharmaceutical composition, and iii) mixing the one or more further component of ii) with the 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) and/or physiologically acceptable salt(s) thereof of i)).

24. A method for inhibiting or reducing the absorption of free fatty acids in the small intestine comprising administering a compound of claim 12 and/or a physiologically acceptable salt thereof to a human in need thereof.

25. The method of claim 24, wherein the free fatty acids are selected from the group consisting of saturated fatty acids with a chain length of more than 4 carbon atoms, preferably of the group consisting of butanoic acid, pentanoic acid, hexanoic acid, heptanoic aid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, heneiconanoic acid, docosanoic acid, tetracosanoic acid, hexacosanoic acid, octacosanoic acid, triacontanoic acid, dotriacontanoic acid, and tetratriacontanoic acid.

26. The method of claim 24, wherein the compound is 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) ##STR00083## or a physiologically acceptable thereof.

27. A method for inhibiting or reducing the absorption of free fatty acids in the small intestine comprising administering a pharmaceutical composition of claim 20 to a human in need thereof.

28. The method of claim 27, wherein the free fatty acids are selected from the group consisting of saturated fatty acids with a chain length of more than 4 carbon atoms, preferably of the group consisting of butanoic acid, pentanoic acid, hexanoic acid, heptanoic aid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid, heneiconanoic acid, docosanoic acid, tetracosanoic acid, hexacosanoic acid, octacosanoic acid, triacontanoic acid, dotriacontanoic acid, and tetratriacontanoic acid.

29. The method of claim 24, wherein the compound is 2-ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23) ##STR00084## or a physiologically acceptable thereof.

Description

EXAMPLES

Example 1: Synthesis of 2-Ethylbutyl-2-(4-hydroxy-3-methoxy-phenyl)acetate (23)

[0081] ##STR00027##

[0082] Homovanillic acid (2.0 g) is provided with 2-ethyl-1-butanol (equimolar) in toluene (100 mL), concentrated sulphuric acid (0.1 g) is added and heated for 5 h at the water separator until boiling. It was washed twice with saturated aqueous NaHCO.sub.3 solution, diluted with 50 mL acetic acid, washed once with water or electively saturated aqueous NaHCO.sub.3 solution and the solvent was removed in the vacuum. The product was obtained after column chromatographic purification on silica gel with a yield of approximately 45%.

[0083] .sup.1H-NMR (400 MHz, CDCl.sub.3): =6.85 (d, J=8.1 Hz, 1H), 6.81 (d, J=1.9 Hz, 1H), 6.76 (dd, J=8.1, 1.9 Hz, 1H), 5.56 (s, 1H), 4.01 (d, J=5.8 Hz, 2H), 3.88 (s, 3H), 3.53 (s, 2H), 1.49 (h, J=6.2 Hz, 1H), 1.38-1.25 (m, 4H), 0.86 (t, J=7.5 Hz, 6H).

[0084] .sup.13C-NMR (100 MHz, CDCl.sub.3): =10.97 (2C), 23.26 (2C), 40.26, 41.14, 55.86, 66.86, 111.68, 114.29, 122.12, 125.98, 144.67, 146.41, 172.07.

[0085] GCMS: m/z (%)=266 [M.sup.+] (28), 182 (18), 137 (100), 122 (8), 107 (2), 94 (6), 85 (3), 77 (2), 66 (5), 57 (4), 43 (28).

Example 2: Analysis of the Intestinal Fatty Acid Resorption

[0086] The resorption of free fatty acids in differentiated Caco-2-cells was analysed with the QBT Fatty Acid Uptake Kit (Molecular Devices Corporation, Germany), which uses the fluorescent fatty acid analogue BODIPY-dodecanoic acid. For preparing the assay, the differentiated Caco-2-cells are subjected to a one hour incubation in serum-free medium at standard cell culture conditions of a hunger phase. Subsequently, the test substances were added at 1 or 100 M, diluted in Hank's balanced salt solution (HBSS of Lonza, Biozym-order number 882010)-buffer, treated with 20 mM HEPES (diluted from a 1M solution of Gibco, Thermo Fisher-order number 15630056) (in the following described as HBSS/HEPES-buffer). Controls were only treated with HBSS/HEPES-buffer. After a 30 minute preincubation at 37 C., the fluorescent fatty acid analogue was added, which was diluted in HBSS/HEPES-buffer (supplemented with 0.2% fatty acid free BSA [Sigma Aldrich, Germany]). The fluorescence signals were measured after excitation with 485 nm at an emission wavelength of 515 nm during a time of 1 h in a microtiter plate-reader (Synergy; BioTek, Germany). Starting from a time-signal-intensity curve resulting from the measurement, the area under the curve (AUC) was calculated to determine the cellular fatty acid resorption after treatment with the substances. The results obtained thereby are indicated as percent related to the control treatment (s. table 1).

TABLE-US-00001 No Name AUC 1 M AUC 100 M Structure 3 1-Ethylbutyl 2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 87.12 62.48 [00028] 7 Homovanillic acid isopropyl ester 91.59 61.61 [00029] 8 Homovanillic acid sec- butyl ester 92.02 61.9 [00030] 12 1-Methylpentyl 2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 89.55 53.26 [00031] 15 [(1R,2S,5R)-2- Isopropyl-5-Methyl- Cyclohexyl] 2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 95.48 58.06 [00032] 23 2-Ethylbutyl 2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 99.73 62.15 [00033]

[0087] Table 1: Results of the measurement of the inhibition of the fatty acid resorption in Caco-2-cells. The calculated area under the curve (AUC) is shown for tests at each 1 and 100 M substance used (as percent of the vehicle treated control).

Example 2: Structure-Effect-Analysis

[0088] With the test for measurement shown in example 2, in total 25 compounds of formula (I) (as described herein) were measured for their inhibitory activity regarding the fatty acid resorption in Caco-2-cells for each two concentrations (1 and 100 M) in triple determination. The obtained activity data was subsequently used for a structure-effect-analysis by using the software-package StarDrop (Optibrium Ltd) and Vortex (Dotmatics Ltd.). Thereby, an R-group analysis with the basic structure according to formula (II) was performed. Here it was found that especially such compounds, in which R1 is branched, have a particularly good inhibition of the fatty acid resorption in the cellular test system.

##STR00034##

Results:

[0089]

TABLE-US-00002 No Name AUC 1 M AUC 100 M R1 12 1-Methylpentyl-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 89.55 53.26 [00035] 15 [(1R,2S,5R)-2- Isopropyl-5-Methyl- Cyclohexyl]-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 95.48 58.06 [00036] 7 Homovanillic acid isopropyl ester 91.59 61.61 [00037] 8 Homovanillic acid sec- butyl ester 92.02 61.9 [00038] 23 2-Ethylbutyl-2-(4- Hydroxy-3-methoxy- phenyl)acetate 99.73 62.15 [00039] 3 1-Ethylbutyl-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 87.12 62.48 [00040] 14 1-Methylhexyl 2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 93.38 67.5 [00041] 9 Homovanillic acid isobutyl ester 100 68.01 [00042] 11 2-Methylbutyl-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 98.97 79.02 [00043] 4 3-Methylbut-2-Enyl 2- (4-Hydroxy-3-Methoxy- Phenyl)acetate 101.2 80.92 [00044] 10 Isopentyl-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 99.85 82.65 [00045] 17 Homovanillic acid propyl ester 101.2 89.65 [00046] 6 3-Z-Homovanillic acid hexene ester 99.86 90.36 [00047] 18 Homovanillic acid butyl ester 102.2 90.69 [00048] 20 Hexyl-2-(4-Hydroxy- 3-Methoxy- Phenyl)acetate 101.9 91.42 [00049] 13 Heptyl-2-(4-Hydroxy- 3-Methoxy- Phenyl)acetate 103.3 92.68 [00050] 19 Homovanillic acid pentyl ester 100.8 92.9 [00051] 16 Ethyl homovanillate 104.7 93.84 [00052] 2 [(E)-Cinnamyl]-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 97.57 94.59 [00053] 5 [(E)-Hex-2-Enyl]-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 100.7 96.53 [00054] 1 2-Phenylethyl-2-(4- Hydroxy-3-Methoxy- Phenyl)acetate 102.7 103.2 [00055]

APPLICATION EXAMPLES

Application Example 1: Refreshing Drinks (Containing Sugar, Calorie Reduced, Calorie Free)

[0090]

TABLE-US-00003 Ingredient Amount in wt.-% Composition A B C D E F G Sugar 10 10 7 8 7 (Sucrose) Glucose/Fructose-Syrup of 10 corn, containing 55 wt.-% fructose Rebaudioside A 95% 0.02 0.05 Citric acid 0.15 0.15 0.06 0.15 0.15 0.15 0.15 Phosphoric acid 0.07 Caramel 0.14 Caffeine 0.01 Lemon aroma 0.1 0.05 0.1 0.1 0.1 0.1 Lime aroma 0.05 Drink emulsion, cola type 0.05 Phloretin 0.002 0.003 0.002 0.001 Hesperetin 0.001 0.002 0.002 Extract of Rubus 0.01 suavissimus, containing 5 wt.-% Rubusoside related to the total weight of the extract Homoeriodictyol sodium salt 0.005 0.005 [(1R,2S,5R)-2-Isopropyl-5- 0.003 0.001 0.005 0.01 0.0025 0.001 0.005 Methyl-Cyclohexyl]-2-(4-Hydroxy-3-Methoxy- Phenyl)acetate Eriodictyol 0.0100 0.0100 0.0100 0.0100 Water Ad 100

[0091] The ingredients were mixed in the listed order and water was filled up to 100%. The mixtures are filled into glass bottles and are carbonized.

Application Example 2: Use in a Chewing Gum

[0092]

TABLE-US-00004 Com- Amount in wt.-% pound Ingredient A B A Chewing gum base, Company 30.4899 30.49999 Jagum T B Sorbit, pulverized 39.00 39.00 Isomalt (Palatinit GmbH) 9.50 9.50 Xylite 2.00 2.00 Mannite 3.00 3.00 Aspartam 0.10 0.10 Acesulfam K 0.10 0.10 Emulgum (Colloides 0.30 0.30 Naturels, Inc.) C Sorbitol, 70% 14.00 14.00 Glycerine 1.00 1.00 D Peppermint aroma 0.5 0.5 1-Methylpentyl-2-(4-Hydroxy- 0.01 0.005 3-Methoxy-Phenyl)acetate Eriodictyol 0.0100

[0093] Compounds A to D are mixed and kneaded intensively. The raw mass can be processed e.g. in form of small stripes into ready-to-eat chewing gums.

Application Example 3: Use in Hard Caramels

[0094]

TABLE-US-00005 Amount (wt.-%) Ingredient A B C D Sugar 74.50 Palatinite, type M 74.00 75.50 75.00 Citric acid 0.5 1.0 0.5 Dye, yellow 0.01 Dye, red 0.01 Dye, blue 0.01 0.01 Peppermint aroma 0.1 0.1 Lemon aroma 0.1 Red fruit aroma 0.1 Rebaudioside A 98% 0.040 0.040 Balansine A according to 0.005 0.010 0.005 [SY317] Hesperetin 0.001 0.001 Phloretin 0.002 2-Ethylbutyl-2-(4-Hydroxy-3- 0.01 0.0025 0.05 0.01 Methoxy-Phenyl)acetate Eriodictyol 0.0100 Water ad 100 ad 100 ad 100 ad 100

[0095] Palatinite or, respectively the sugar were optionally mixed with water after adding the citric acid and the mixture was molten at 165 C. and subsequently cooled down to 115 C. The aroma and the other components were added and poured into forms after mixing, removed from the forms after solidifying and subsequently packed separately.

Application Example 4: Fat-Reduced Yoghurts

[0096]

TABLE-US-00006 Composition (amount in wt.-%) Ingredient A B C D Sucrose 10 8 6 Rebaudioside A 98% 0.050 Extract of Rubus suavissimus, 0.010 0.010 containing 5 wt.-% Rubusoside related to the total weight of the extract, e.g. of PlantExtrakt Hesperetin 0.001 0.001 0.002 Phloretin 0.002 0.002 Homoeriodictyol sodium salt 0.005 [(1R,2S,5R)-2-Isopropyl-5-Methyl- 0.01 0.01 0.005 0.01 Cyclohexyl]-2-(4-Hydroxy-3-Methoxy- Phenyl)acetate Eriodictyol 0.0100 0.0100 Yoghurt, 0.1% Fat Ad 100%

[0097] The ingredients were mixed and cooled down to 5 C.

Application Example 5: Fruit Gums

[0098]

TABLE-US-00007 Composition (amount in wt.-%) Ingredient A B Sucrose 34.50 8.20 Glucose syrup, DE 40 31.89 30.09 Iso Syrup C* Tru Sweet 1.50 2.10 01750 (Cerestar GmbH) Gelatine 240 Bloom 8.20 9.40 Polydextrose (Litesse 24.40 Ultra, Danisco Cultor GmbH) Yellow and red dye 0.01 0.01 Citric acid 0.20 Cherry aroma, containing 1 0.10 wt.-% Hesperetin and 0.3 wt.-% Phloretin related to the aroma Homovanillic acid sec 0.01 0.01 butyl ester Eriodictyol 0.0100 Water ad 100 ad 100

[0099] Polydextrose is a polysaccharide with a low calorific value, which has not a sweet taste.

Application Example 6: Fruit Juices and Fruit Juice Drinks

[0100]

TABLE-US-00008 Ingredient Amount in wt.-% Composition A B C D Apple juice concentrate 10-fold 10 10 10 Recovery aroma of apple juice 0.1 0.1 0.1 concentrate Orange juice concentrate 20-fold 5 Recovery aroma of orange juice 0.05 concentrate Water ad ad ad ad 100 100 100 100 Ascorbic acid 0.05 0.05 [(1R,2S,5R)-2-lsopropyl-5-Methyl- 0.01 0.01 0.01 0.01 Cyclohexyl] 2-(4-Hydroxy-3-Methoxy- Phenyl)acetate

Application Example 7: Milk Mixture Drink on a Dry Base

[0101]

TABLE-US-00009 Ingredient Amount in [g] Composition A B C D E F G Sugar, fine 5 5 5 5 5 5 5 Homovanillic 0.03 0.03 0.03 0.03 0.02 0.015 0.03 acid sec butyl ester, 10% Aroma type 0.2 0.2 0.2 0.2 Cappuccino, spray dried Aroma type 0.1 0.1 0.1 strawberry, spray dried Red beet dye powder, 0.1 0.08 0.1 spray dried Caramel 0.15 0.15 0.15 0.15 Xanthan 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Skimmed milk 10 10 10 10 powder Milk powder, lactose 10 10 reduced (Fa. Omira, Ravensburg) Lupinen protein 5 powder

[0102] The ingredients were mixed and packed under protective gas or in a vacuum bag. For use, the powder is stirred into 100 mL water (room temperature) and then drunk.

Application Example 8: Spray Dried Composition as Semi-Finished Product for Aromatizing Finished Products According to the Invention

[0103]

TABLE-US-00010 Ingredient Amount in wt.-% Drinking water 60.8% Maltodextrin from wheat 24.3% Gum Arabicum 6.1% [(1 R,2S,5R)-2-Isopropyl-5-Methyl-Cyclohexyl]- 8.8% 2-(4-Hydroxy-3-Methoxy-Phenyl)acetate

[0104] The drinking water is provided in a container and the maltodextrin and gum arabicum are dissolved therein. Subsequently, the [(1R,2S,5R)-2-Isopropyl-5-Methyl-Cyclohexyl]-2-(4-Hydroxy-3-Methoxy-Phenyl)acetate is emulsified with a Turrax. The temperature of the spray solution should not exceed 30 C. The mixture is then spray dried (set temperature input: 185-195 C.; set temperature output: 70-75 C.).

[0105] The spray dried semi-finished product contains 18-22% [(1R,2S,5R)-2-Isopropyl-5-Methyl-Cyclohexyl]-2-(4-Hydroxy-3-Methoxy-Phenyl)acetate and can be used for producing a composition according to the invention as described herein.

Application Example 9: Use in a Soy Drink

[0106] The compound [(1R,2S,5R)-2-Isopropyl-5-Methyl-Cyclohexyl]-2-(4-Hydroxy-3-Methoxy-Phenyl)acetate was dissolved in ethanol and added to a soy milk of a local supermarket. The mixture was then stirred in a beaker together with the milk aroma.

TABLE-US-00011 Ingredient Amount in wt.-% Soy milk (local supermarket) 99.8% Milk aroma (Symrise) 0.1% 10% [(1R,2S,5R)-2-Isopropyl-5-Methyl-Cyclohexyl]- 0.1% 2-(4-Hydroxy-3-Methoxy-Phenyl)acetate

Application Example 10: Whey Protein Drink

[0107] Production of a fruit whey protein drink according to the recipe below, with subsequent homogenisation and pasteurisation.

TABLE-US-00012 Ingredient Amount in wt.-% Whey protein isolate 8% Fruit juice concentrate mixture (mango, 10% banana, carrot, orange) Citric acid 50% 0.2% Pectin 0.4% Vitamin mixture 0.01% Mineral salt mixture 1% 10% [(1R,2S,5R)-2-Isopropyl-5-Methyl- 0.1% Cyclohexyl]-2-(4-Hydroxy-3-Methoxy- Phenyl)acetate Mango Aroma (Symrise) 0.05% Drinking water Ad 100%

Application Example 11: Drink Containing High Amounts of Protein (Sports Nutrition)

[0108] The dry ingredients are mixed and subsequently dissolved in drinking water.

TABLE-US-00013 Ingredient Amount in wt.-% Whey protein isolate (min. 88% protein TS) 8% Amino acid mixture (45% L-Leucine; 30% L- 1% Valine, 25% L-Isoleucine) Citric acid 0.1% Sucralose 0.007% Orange dry aroma (Symrise) 0.1% 10% [(1R,2S,5R)-2-Isopropyl-5-Methyl- 0.1% Cyclohexyl]-2-(4-Hydroxy-3-Methoxy- Phenyl)acetate Drinking water Ad 100%

Application Example 12: Dietary Foodstuff for Special Medical Purposes (FSMP)

[0109] Production of an UHT-drink according to the recipe below.

TABLE-US-00014 Ingredient Amount in wt.-% Whey protein concentrate (min. 12% 80% protein TS) Drinking water Ad 100% Glucose syrup 10% Vegetable oils 4% Sucrose 2% Maltodextrin 1.5% Vitamin mixture 0.05% Mineral salt mixture 2% Vanilla aroma (Symrise) 0.2% Lecithin 0.1% Citric acid 0.05% 10% 2-Ethylbutyl-2-(4-hydroxy-3- 0.1% methoxy-phenyl)acetate in ethanol