COMBINATION OF NATURAL SUBSTANCES COMPRISING AT LEAST ONE GLYCYRRHETINIC ACID AND AT LEAST ONE GUGGULSTERONE, AND USE THEREOF FOR COSMETIC APPLICATIONS

Abstract

The present invention relates to a combination of natural substances comprising at least one glycyrrhetinic acid and at least one guggulsterone, and to the use thereof for cosmetic applications. The present invention relates especially to vesicles (especially for topical application) comprising at least one glycyrrhetinic acid and at least one guggulsterone. The vesicles are preferably added to a cream, a lotion or a gel, the resulting cream, lotion or gel being used for the cosmetic and/or dermatological treatment of the skin and/or for the prophylaxis of the appearance of cellulite and/or ageing skin and/or for the treatment of changes in subcutaneous fatty or connective tissue, for example lipomas and other non-specific subcutaneous fat deposits, or for the regression or reduction of fat pads which are not caused by disease, such as, for example, fat pads in the face and neck region, for example lachrymal sacs, etc.

Claims

1. Vesicles comprising: a) at least one glycyrrhetinic acid or a salt or an ester thereof; b) at least one guggulsterone; and c) either: c1) phosphatidylcholine, or c2) at least one emulsifier from the food additives group and at least one monoester of a long-chained fatty acid.

2. Vesicles according to claim 1, comprising: a) at least one glycyrrhetinic acid or a salt or an ester thereof; b) at least one guggulsterone; and c) phosphatidylcholine.

3. Vesicles according to claim 1, comprising: a) at least one glycyrrhetinic acid or a salt or an ester thereof; b) at least one guggulsterone; and c) at least one emulsifier from the food additives group and at least one monoester of a long-chained fatty acid.

4. Vesicles according to claim 1, wherein the phosphatidylcholine originates from soy lecithin or sunflower lecithin.

5. Vesicles according to claim 1, wherein the phosphatidylcholine is used in the form of soy lecithin or sunflower lecithin.

6. Vesicles according to claim 3, which further comprise a plant oil.

7. Vesicles according to claim 1 wherein the at least one glycyrrhetinic acid or the salt or the ester thereof is chosen from 18-glycyrrhetinic acid and/or 18-glycyrrhetinic acid or one or more salt(s) or ester(s) thereof, and in that the at least one guggulsterone is selected from (Z)-guggulsterone and/or (E)-guggulsterone.

8. Vesicles according to claim 1 wherein the at least one glycyrrhetinic acid or the salt or the ester thereof is used in the form of Glycyrrhiza glabra or in the form of extract from Glycyrrhiza glabra and/or in the form of a pure chemical substance and/or in the form of salts or esters thereof, and/or in that the at least one guggulsterone is used in the form of guggul lipid or in the form of extract from guggul lipid and/or in the form of a pure chemical substance.

9. Vesicles according to claim 1 wherein the at least one emulsifier from the food additives group is selected from the food additives E471, E472a, E472b, E472c, E472d, E472e, E472f, E473, E474, E475, E476 and E477.

10. Vesicles according to claim 1, comprising: 0.1-0.5 part by weight of a glycyrrhetinic acid or of a salt or an ester thereof; 0.1-0.5 part by weight of a guggulsterone; and 0.5-3 parts by weight of at least one surfactant; per 10 parts by weight of phosphatidylcholine.

11. Vesicles according to claim 1, comprising: 15-20% (v/v) seed oil of an edible plant; 2.5-10% (w/v) emulsifier(s) from the food additives group; 2.5-5% (w/v) of at least one monoester of a long-chained fatty acid; 10-20% (v/v) ethanol; 0.1-10% (w/v) 18-glycyrrhetinic acid; and 0.1-10% (w/v) (Z)-guggulsterone; made up to 100% with water.

12. Vesicles according to claim 1, comprising: 7-17.5% (w/v) emulsifier(s) from the food additives group; 3-7.5% (w/v) of at least one monoester of a long-chained fatty acid; 10-20% (v/v) ethanol; 0.1-10% (w/v) 18-glycyrrhetinic acid; and 0.1-10% (w/v) (Z)-guggulsterone; made up to 100% with water.

13. Cream, lotion or gel comprising vesicles according to claim 1.

14. Cream, lotion or gel according to claim 13, characterised in that the at least one glycyrrhetinic acid or the salt or the ester thereof and the at least one guggulsterone are each present in an amount of 0.01-10% (w/w), preferably 0.1-5% (w/w), based on the total weight of the cream, lotion or gel.

15. Vesicles comprising: 0-5% (w/w) glycyrrhetinic acid or a salt or an ester thereof 0-5% (w/w) guggulsterone 5-25% (w/w) abs. ethanol 1-30% (w/w) ethyl oleate 0-30% (w/w) plant oil (for example sunflower oil, soybean oil, rape oil) 0.5-5% (w/w) diglyceryl monooleate 0-5% (w/w) Imwitor 375 (glyceryl citrate/lactate/linoleate/oleate) ad 100% purified water; wherein the vesicles comprise at least glycyrrhetinic acid or a salt or an ester thereof or guggulsterone.

16. Vesicles comprising: 0-5% (w/w) glycyrrhetinic acid or a salt or an ester thereof 0-5% (w/w) guggulsterone 5-25% (w/w) abs. ethanol 1-10% (w/w) ethyl oleate 5-25% (w/w) Imwitor 375 (glyceryl citrate/lactate/linoleate/oleate) ad 100% purified water; wherein the vesicles comprise at least glycyrrhetinic acid or a salt or an ester thereof or guggulsterone.

17. Vesicles comprising: 0-5% (w/w) glycyrrhetinic acid or a salt or an ester thereof 0-5% (w/w) guggulsterone 10-15% (w/w) jojoba oil 15-25% (w/w) cetyl palmitate 0.2-1.0% (w/w) Inutec SP1 1-3% (w/w) TEGO Care PS ad 100% purified water; wherein the vesicles comprise at least glycyrrhetinic acid or a salt or an ester thereof or guggulsterone.

18. Formulation of the vesicles according to claim 1 as a cream, a lotion or a gel for use in the cosmetic and/or dermatological treatment and/or prophylaxis of cellulite and/or for the treatment and/or prophylaxis of the appearance of ageing skin.

19. Face mask comprising at least one glycyrrhetinic acid or a salt or an ester thereof and at least one guggulsterone.

20. Face mask comprising a vesicle according to claim 1.

21. Face mask comprising at least one glycyrrhetinic acid or a salt or an ester thereof and at least one guggulsterone each in an amount of 0.01-5% (w/w), preferably 0.1-2.5% (w/w), based on the total weight of the face mask.

22-23. (canceled)

24. Plaster or patch comprising at least one glycyrrhetinic acid or a salt or an ester thereof and at least one guggulsterone.

25. Plaster or patch comprising a vesicle according to claim 1.

26. Composition comprising: A) vesicles comprising: a) at least one glycyrrhetinic acid or a salt or an ester thereof; and c) either: c1) phosphatidylcholine, or c2) at least one emulsifier from the food additives group and at least one monoester of a long-chained fatty acid; and B) vesicles comprising: b) at least one guggulsterone; and d) either: d1) phosphatidylcholine, or d2) at least one emulsifier from the food additives group and at least one monoester of a long-chained fatty acid.

27. Cream, lotion, gel, plaster, patch or face mask comprising a composition according to claim 26.

28. Formulation of the composition according to claim 26 as a cream, a lotion or a gel for use in the cosmetic and/or dermatological treatment and/or prophylaxis of cellulite and/or for the treatment and/or prophylaxis of the appearance of ageing skin.

29-30. (canceled)

31. A method for treatment of prophylaxis of ageing or stressed skin comprising administering to a subject vesicles according to claim 1.

32. A method of treatment of a changes in subcutaneous fatty or connective tissue comprising administering to a subject vesicles according to claim 1 or of a combination of at least one glycyrrhetinic acid or a salt or an ester thereof and at least one guggulsterone.

33. The method of claim 32 wherein the changes in subcutaneous fatty or connective tissue are lipoedema, lipoma, lipomatosis of the abdominal wall, dermatopanniculosis deformans, pseudogynecomastia, buffalo hump in HIV patients, and non-specific subcutaneous fat deposits, or in the regression or reduction of fat pads which are not caused by disease, such as, for example, fat pads in the face and neck region (for example lachrymal sacs, nasolabial folds, flabby cheeks, double chin, etc.), or in after-treatment following liposuction.

34. A method for treatment of prophylaxis of ageing or stressed skin comprising administering to a subject a composition of claim 26.

35. A method of treatment of a changes in subcutaneous fatty or connective tissue comprising administering to a subject a composition of claim 26.

36. The method of claim 35 wherein the changes in subcutaneous fatty or connective tissue are lipoedema, lipoma, lipomatosis of the abdominal wall, dermatopanniculosis deformans, pseudogynecomastia, buffalo hump in HIV patients, and non-specific subcutaneous fat deposits, or in the regression or reduction of fat pads which are not caused by disease, such as, for example, fat pads in the face and neck region (for example lachrymal sacs, nasolabial folds, flabby cheeks, double chin, etc.), or in after-treatment following liposuction.

Description

EXAMPLES

[0187] Cell Culture

[0188] The 3T3-L1 mouse fibroblasts were cultivated in Dulbecco's modified Eagle's medium (DMEM) incl. 10% foetal calf serum (FCS) and 2 mM L-glutamine at 37 C., 95% humidity and 5% CO.sub.2.

[0189] Adipocyte differentiation and maturation was induced as described (Yang J. Y. et al., Obesity 2008, 16, 16-22; Shugart E. C. and Umek R. M., Cell Growth & Differentiation 1997, 8, 1091-1098). The cells were stimulated not only with dexamethasone, as is generally conventional, but also with cortisol, which is more physiological.

[0190] The cells were seeded into 96-well plates and cultivated to confluence. Two days after reaching cell confluence (D0=day 0), cell differentiation was induced by adding DMEM with 10% FCS, 167 nM insulin, 0.5 M IBMX and 1 M dexamethasone or 200 nM cortisol for two days (D2). The cells were then cultivated for a further two days in DMEM with 10% FCS and 167 nM insulin (D4), followed by cultivation in DMEM/10% FCS for a further four days (D8). Ultimately, >20-30% of the cells were mature adipocytes with accumulated lipid stores.

[0191] Determination of the Cellular Lipid Content

[0192] As an indicator for the degree of adipogenesis, the lipid content of the cells (intracellular lipid droplets) was detected by means of the lipophilic colour reagent Nile red, as described (Yang J. Y. et al., Obesity 2008, 16, 16-22; Greenspan P., The Journal of Cell Biology 1985, 100, 965-973). 3T3-L1 cells (5,000-10,000 cells/well), after reaching confluence, were cultivated for a further two days in 96-well plates (D0). The cells were then treated with guggulsterone and/or glycyrrhetinic acid, individually or in combination, for days D0-D2, D2-D4, D4-D6 and D0-D6 of the adipogenesis (concentration range: 1-200 M). The medium, with or without test substance(s), was changed or renewed every two days. Cells treated as follows served as controls: (1) pure cell culture medium (undifferentiated control), (2) pure differentiation medium (untreated control), and (3) DMSO, corresponding to the highest DMSO concentration in the test batches, in differentiation medium (DMSO control).

[0193] On day 6 (D6), the intracellular lipid accumulation (lipid droplets) was quantified by means of a Nile red assay. To that end, the cell medium was discarded and the cells were washed with 100 l/well of PBS (pH 7.4). The cells were then incubated for 20 minutes at room temperature with 50 l/well of Nile red in PBS (10 g/ml). The lipid content was determined fluorometrically using a Synergy 2 plate reader (BioTek, Winooski, USA) (excitation: 485 nm, emission: 560 nm, mirror: 550 nm). Nile red selectively stains neutral lipids, for example triacylglycerides in intracellular droplets.

[0194] For analyses by fluorescence microscopy, the cells were treated on Lab-Tek chamber slides (Nunc, Langenselbold, Germany) as described above and incubated for days D2-D4 of the adipogenesis with guggulsterone and/or glycyrrhetinic acid (50 or 100 M; individually or in equimolar combination). The incubation medium was then discarded and the cells were washed with PBS and stained with Nile red (10 g/ml) and DAPI (1 g/ml) in 50 l/well of PBS for 20 minutes at room temperature. After removal of the staining solution, the cells were washed with PBS and fixed with 4% paraformaldehyde in PBS for 30 minutes at room temperature. Finally, the cells were washed three times with PBS and mounted on the object slide by means of Fluorescence Mounting Medium (Dako, Carpinteria, USA). The fluorescence microscopy images were taken by using a Zeiss Axio Observer.Z1 with ApoTome (Carl Zeiss Microlmaging, Jena, Germany) using the DAPI and GFP filter settings.

[0195] Cell Viability Assay

[0196] The cell viability of mature adipocytes after treatment with a test compound was measured by means of a fluorimetric Resazurin-based assay. Vital, that is to say metabolically active, cells are capable of converting Resazurin into the fluorescent derivative Resorufin (Strotmann U. J. et al., Ecotox. Environ. Safety 1993, 25, 79-89).

[0197] 3T3-L1 cells were seeded into 96-well plates (5,000-10,000 cells/well) and, as described above, cultivated to maturity (D8). On D8, the mature adipocytes were incubated for 24 hours under standard culture conditions with guggulsterone and/or glycyrrhetinic acid (1-250 M). Cells treated as follows served as controls: (1) pure cell culture medium (undifferentiated control), (2) pure differentiation medium (untreated control), (3) DMSO, corresponding to the highest DMSO concentration in the test batches, in differentiation medium (DMSO control), and (4) 150 g/ml digitonin in DMEM (cell death control). After 24 hours, the incubation medium was discarded and the cells were washed with 100 l/well of DMEM and then incubated for 2 hours under standard culture conditions with 50 l/well of Resazurin solution (60 M in DMEM). Finally, the Resorufin fluorescence was detected by means of a Synergy 2 plate reader (BioTek, Winooski, USA) (excitation: 540 nm, emission: 590 nm, mirror: 550 nm).

[0198] Apoptosis Assay

[0199] In order to evaluate a possible induction of apoptosis in mature adipocytes as a result of the treatment with (Z)-guggulsterone and/or glycyrrhetinic acid, a Caspase-Glo 3/7 assay kit (Promega, Mannheim, Germany) was used.

[0200] 3T3-L1 cells were seeded into 96-well plates (5,000-10,000 cells/well) and, as described above, cultivated to maturity (D8). On D8, the mature adipocytes were incubated for 24 hours under standard culture conditions with guggulsterone and/or glycyrrhetinic acid (1-250 M). Cells treated as follows served as controls: (1) pure cell culture medium (undifferentiated control), (2) pure differentiation medium (untreated control), and (3) DMSO, corresponding to the highest DMSO concentration in the test batches, in differentiation medium (DMSO control). After 24 hours, the incubation medium was discarded, the cells were washed with 100 l/well of DMEM, and then 150 l/well of Caspase-Glo 3/7 reagent in DMEM (1:1, v/v) were added. After incubation for 2 hours at room temperature, the luminescence signal of the reagent was detected by means of a Synergy 2 plate reader (BioTek, Winooski, USA).

[0201] Lipolysis Assay

[0202] Lipolysis of mature adipocytes as a result of the treatment with guggulsterone and/or glycyrrhetinic acid was detected by means of a glycerol release assay. For this purpose, the glycerol released into the cell medium as a result of the lipolysis of the cells was quantified using a free glycerol staining reagent (Cayman Chemical, Ann Arbor, USA).

[0203] 3T3-L1 cells were seeded into 96-well plates (5,000-10,000 cells/well) and, as described above, cultivated to maturity (D8). On D8, the mature adipocytes were incubated for 24 hours under standard culture conditions with guggulsterone and/or glycyrrhetinic acid (1-250 M). Cells treated as follows served as controls: (1) pure cell culture medium (undifferentiated control), (2) pure differentiation medium (untreated control), and (3) DMSO, corresponding to the highest DMSO concentration in the test batches, in differentiation medium (DMSO control).

[0204] Following the incubation, 25 l of the cell medium of each sample were transferred into a corresponding well of a new 96-well plate and incubated with 90 l of the free glycerol staining reagent for 15 minutes at room temperature. 25 l samples with 90 l of aqua dest. instead of the reagent served as the measurement reference. Finally, the content of released glycerol was determined on the basis of the absorption at 540 nm by means of a Synergy 2 plate reader (BioTek, Winooski, USA).

[0205] Lipid Content in Pre-Adipocytes

[0206] The lipid content, that is to say the storage of triacylglycerides in intracellular lipid droplets, is an indicator for the degree of adipogenesis. We used a Nile red assay to study the effects of (Z)-guggulsterone and 18-glycyrrhetinic acid, respectively, on the dexamethasone- or cortisol-stimulated adipogenesis of 3T3-L1 mouse fibroblasts. Since the staining reagent Nile red, upon excitation at 485 nm and fluorescence detection at 560 nm, is very selective for neutral lipids, it was thus possible specifically to measure the intracellular accumulation of triacylglycerides during advancing adipogenesis.

[0207] The period of treatment within the 6-day differentiation period of the adipocytes was very important for the effects of (Z)-guggulsterone or 18-glycyrrhetinic acid on cellular lipid accumulation which are to be observed. Both compounds, (Z)-guggulsterone and 18-glycyrrhetinic acid, inhibited the lipid accumulation of the cells to the greatest extent when they were applied over the entire 6-day differentiation period. Microscopic analyses illustrated very clearly the effects of (Z)-guggulsterone and 18-glycyrrhetinic acid on the lipid content of 3T3 pre-adipocytes which were treated with 100 M (Z)-guggulsterone and 100 M 18-glycyrrhetinic acid, respectively, over the period D0-D6 of the adipogenesis (stimulation with 1 M dexamethasone). Stimulated but untreated cells served as reference and showed a high degree of lipid storage. By contrast, after treatment of the cells with (Z)-guggulsterone and 18-glycyrrhetinic acid, respectively, significantly fewer and smaller lipid droplets were to be detected.

[0208] For the most part, this effect was induced in days D0-D2, that is to say the initial phase of the adipocyte differentiation. The reduction of the lipid content of correspondingly treated 3T3 pre-adipocytes, 0-100 M (Z)-guggulsterone and 18-glycyrrhetinic acid, respectively, in the period D0-D2, is summarised in the following table:

TABLE-US-00001 TABLE 1 (Z)-Guggulsterone 18-Glycyrrhetinic acid 0 10 40 100 0 10 40 100 M M M M M M M M Lipid 100% 71% 26% 5% 100% 98% 91% 7% content* *normalised against unstimulated/untreated cells

[0209] On day 6 of the adipogenesis (D6), the accumulation of intracellular lipid droplets was measured fluorometrically by means of a Nile red assay (excitation: 485 nm; emission: 560 nm; 550 nm mirror). The data were normalised and the lipid accumulation is given in percent; unstimulated cells were used as 0% reference, and stimulated but untreated cells were used as 100% reference.

[0210] On treatment of the cells for the entire 6-day adipocyte differentiation (D0-D6), an IC.sub.50 value for the inhibition of cellular lipid accumulation of 5 M was obtained for (Z)-guggulsterone and of 20 M for 18-glycyrrhetinic acid. Both compounds, (Z)-guggulsterone and 18-glycyrrhetinic acid, thus inhibit the accumulation of triacylglycerides in 3T3-L1 cells during adipogenesis, but guggulsterone is slightly more potent than glycyrrhetinic acid in this respect. In the activity range of 18-glycyrrhetinic acid (50 M), a synergistic action was additionally detected in conjunction with (Z)-guggulsterone used in an equimolar amount.

[0211] Treatment of the cells in the middle differentiation phase (days D2-D4) likewise brought about good inhibition of lipid accumulation. For stimulation of adipocyte differentiation, cortisol, which is more physiological, was also used instead of the conventional dexamethasone for comparison, no substantial differences being observed as regards the results.

[0212] Cell Viability/Number of Mature Adipocytes

[0213] Fluorometric Resazurin-based cell viability assays were carried out in order to investigate possible effects of a treatment with (Z)-guggulsterone and/or 18-glycyrrhetinic acid on the viability, and thus the number, of mature 3T3 adipocytes. To that end, mature 3T3 adipocytes were stimulated with 1 M dexamethasone and then treated for 24 hours under standard culture conditions with increasing concentrations of (Z)-guggulsterone or 18-glycyrrhetinic acid or of an equimolar mixture of both compounds. Finally, the cell viability, as a measure of the number and fitness of the cells, was measured by means of a Resazurin assay.

[0214] As is shown in FIG. 1, a 24-hour treatment with up to 250 M (Z)-guggulsterone did not impair the cell viability. 250 M 18-glycyrrhetinic acid, on the other hand, reduced the cell viability, that is to say the number of mature adipocytes, by 28% with the same treatment time. Treatment of the cells with equimolar mixtures of both compounds, (Z)-guggulsterone and 18-glycyrrhetinic acid, resulted in a significant effect synergy. The combination of 250 M of each of the two compounds reduced the cell viability by 56%. (Z)-Guggulsteronealthough without effect on its ownappears to be capable of enhancing the cytostatic effect caused by 18-glycyrrhetinic acid on mature adipocytes.

[0215] Induction of Apoptosis in Mature Adipocytes

[0216] Possible reasons for the observed decrease in cell viability may be anti-proliferative effects of the test compound (that is to say induction of a cell cycle arrest), a reduction in the metabolic activity of the cells, or a reduction of the number of vital adipocytes following the induction of apoptosis.

[0217] In order to test whether the effects of 18-glycyrrhetinic acid, either alone or in equimolar combination with (Z)-guggulsterone, in reducing cell viability may be based on the induction of apoptosis, correspondingly treated adipocytes were investigated in respect of an activation of the effector caspases 3/7 (in the case of advanced apoptosis). Regardless of the type of adipocyte stimulation, with dexamethasone or with cortisol, (Z)-guggulsterone showed no induction of caspases 3/7. By contrast, treatment of the cells with 250 M of 18-glycyrrhetinic acid for 24 hours brought about an increase in caspase 3/7 activity by a factor of 2.5-3.0 as compared with untreated cells. The equimolar combination of both compounds, (Z)-guggulsterone and 18-glycyrrhetinic acid, showedin line with the results of the viability assaya synergistic effect of the two compounds in respect of caspase activation. The combination of 250 M of each of the two compounds brought about an increase in caspase 3/7 activity by a factor of 3.5-4.0 as compared with untreated cells (FIG. 2).

[0218] In summary, 18-glycyrrhetinic acid inhibits the viability of mature adipocytes by inducing an apoptotic cell death programme as a result of which, inter alia, caspases 3/7 are activated. Although (Z)-guggulsterone on its own is inactive in this context, it is capable of enhancing the effects of 18-glycyrrhetinic acid.

[0219] Lipolysis in Mature Adipocytes

[0220] In order to study a possible degradation of the intracellular triacylglyceride reservoirs in mature adipocytes, that is to say lipolysis, as a result of treatment with (Z)-guggulsterone and/or 18-glycyrrhetinic acid, a glycerol release assay was carried out. The enzymatic degradation of triacylglycerides leads to the production of glycerol, which is membrane-permeable and is thus released into the surrounding culture medium. Free glycerol in the medium can be quantified spectrophotometrically by means of specific staining reagents. After 24 hours' treatment with the equimolar combination (in each case 250 M) of the two compounds, (Z)-guggulsterone and 18-glycyrrhetinic acid, the degradation of intracellular triglycerides had increased by 66% as compared with an untreated control.

[0221] The examples which follow are intended to illustrate exemplary embodiments of the present invention.

Example 1: Flexible Soy-Phosphatidylcholine-Containing Liposomes, Comprising the Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0222] For the preparation of flexible soy-phosphatidylcholine-containing liposomes, soy phosphatidylcholine (Phospholipon 90 G; Lipoid, Ludwigshafen) and surfactants, such as, for example, cholesterol or sodium cholate, as well as 18-glycyrrhetinic acid and (Z)-guggulsterone were mixed in the weight ratio 10/0.5-3/0.1-0.5/0.1-0.5 (w/w/w/w). The preferred formulation comprises Phospholipon 90 G (95% soy phosphatidylcholine), sodium cholate, 18-glycyrrhetinic acid and (Z)-guggulsterone in the ratio 10/1/0.3/0.3 (w/w/w/w). Lipid and surfactant were dissolved in chloroform/MeOH (1:2 v/v) and concentrated to dryness in vacuo at 40 C. overnight in a rotary evaporator. The resulting lipid film was rehydrated (1 h/30 C./200 rpm) with PBS (pH 7.4), which contained the corresponding amounts of glycyrrhetinic acid and guggulsterone, to give a 10% lipid suspension. The suspension was treated with ultrasound for 20 minutes (on/off interval: 10 s) and extruded through a PC filter membrane (100 nm pore size). The vesicle size was analysed by means of dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments GmbH, Herrenberg, Germany; for 5 minutes at room temperature) and was in the range 50-100 nm.

Example 2: Vesicles Based on a Lipidic Emulsifier from the Food Additives Group, a Monoester of a Long-Chained Fatty Acid and a Plant Oil and Comprising an Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0223] For the preparation of oil emulsifier vesicles containing glycyrrhetinic acid and guggulsterone, 15-20% (v/v) of sunflower seed oil (Helianthus annuus); 2.5-10% (w/v) Imwitor 375 (glyceryl citrate/lactate/linoleate/oleate; Cremer Oleo GmbH, Hamburg); 2.5-5% (w/v) polyglyceryl-2 oleate; 10-20% (v/v) ethanol were mixed with 0.1-10% (w/v) of each of 18-glycyrrhetinic acid and (Z)-guggulsterone and made up to 100% with aqua bidest. The preferred formulation comprises 20% (v/v) sunflower seed oil; 5% (w/v) Imwitor 375; 2.5% (w/v) polyglyceryl-2 oleate; 15% (v/v) ethanol; 5% (w/v) 18-glycyrrhetinic acid and 5% (w/v) (Z)-guggulsterone in aqua bidest. The sunflower seed oil, Imwitor 375, polyglyceryl-2 oleate, 18-glycyrrhetinic acid and (Z)-guggulsterone were dissolved at room temperature in ethanol, with shaking (500 rpm). Under constant conditions, aqua bidest. was then added slowly and evenly (200 l/min) to 100% (v/v), and the whole was mixed thoroughly. Finally, the dispersion was vortexed for 5 minutes, treated with ultrasound for 5 minutes (on/off interval: 10 s) and extruded through a PC filter membrane (100 nm pore size). The vesicle size was analysed by means of dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments GmbH, Herrenberg, Germany; for 5 minutes at room temperature) and was in the range 80-100 nm.

Example 3: Vesicles Based on a Lipidic Emulsifier from the Food Additives Group and a Monoester of a Long-Chained Fatty Acid and Comprising an Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0224] For the preparation of emulsifier vesicles containing glycyrrhetinic acid and guggulsterone, 7-17.5% (w/v) Imwitor 375 (glyceryl citrate/lactate/linoleate/oleate; Cremer Oleo GmbH, Hamburg); 3-7.5% (w/v) ethyl oleate; 10-20% (v/v) ethanol were mixed with 0.1-10% (w/v) of each of 18-glycyrrhetinic acid and (Z)-guggulsterone and made up to 100% with aqua bidest. The preferred formulation comprises 10.5% (w/v) Imwitor 375; 4.5% (w/v) Crodamol ethyl oleate (Croda GmbH, Nettetal Kaldenkirchen); 15% (v/v) ethanol; 5% (w/v) 18-glycyrrhetinic acid and 5% (w/v) (Z)-guggulsterone in aqua bidest. Imwitor 375; ethyl oleate; 18-glycyrrhetinic acid and (Z)-guggulsterone were dissolved at room temperature in ethanol, with shaking (500 rpm). Under constant conditions, aqua bidest. was then added slowly and evenly (200 l/min) to 100% (v/v), and the whole was mixed thoroughly. Finally, the dispersion was homogenised at 200 bar for 5 minutes. The vesicle size was analysed by means of dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments GmbH, Herrenberg, Germany; for 5 minutes at room temperature) and was in the range 100-150 nm.

Example 4: Formulation as a Cream

[0225] A cream according to the invention preferably comprises flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 1, which vesicles are incorporated in an amount of 10% (v/w) in a base cream DAC comprising glycerol monostearate 60 4 g; cetyl alcohol 6 g; Miglyol 812 7.5 g; white petroleum jelly (vasilinum album) 25.5 g; Macrogol 20 glyceryl monostearate 7 g; propylene glycol 10 g and aqua bidest. to 100 g. The flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 1 were thereby incorporated homogeneously into the base cream as the last cream component at 40 C.

Example 5: Formulation as a Cream

[0226] A cream according to the invention preferably comprises oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 2, which vesicles are incorporated in an amount of 10% (v/w) into a cream comprising isooctyl laurate 10 g; cetyl stearyl alcohol 21 g; glycerol (85% v/v) 5 g; propyl hydroxybenzoate 0.05 g; methyl hydroxybenzoate 0.15 g; 0.3 g of limonene; 0.3 g of linanool; ethanol (90% v/v) 1.8 mg and aqua bidest. to 100 g. The oil emulsifier vesicles containing 183-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the cream as the last cream component at 40 C.

Example 6: Formulation as a Cream

[0227] A cream according to the invention preferably comprises emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 3, which vesicles are incorporated in an amount of 10% (v/w) into a cream comprising PEG-8 L (polyoxyethylene laurate ester) 15 g; ethyl octanoate 5 g; C12-C15 alkyl benzoate 4.5 g; glycerol 3 g; dimethicone 0.5 g; disodium EDTA 0.1 g and aqua bidest. to 100 g. The emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the cream as the last cream component at 40 C.

Example 7: Formulation as a Cream

[0228] Oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 2 were incorporated in an amount of 10% (v/w) into a cream comprising 1,2-hexanediol 0.5 g; butylmethoxydibenzoylmethane 4.0 g; Butyrospermum parkii butter (shea butter) 6.0 g; C12-C15 alkyl benzoate 2.0 g; Tego Carbomer 140 0.3 g; cetyl palmitate 1.0 g; cetyl alcohol 1.0 g; cetyl stearyl alcohol 1.0 g; dibutyl adipate 3.0 g; ethylhexyl salicylate 4.5 g; glycerol 10.0 g; glyceryl monostearate 2.5 g; hydrogenated coco-glycerides 1.0 g; methylpropanediol 2.0 g; sodium hyaluronate 0.15 g; perfume; phenoxyethanol 0.6 g; phenylbenzimidazole sulfonic acid 2.0 g; sodium stearyl glutamate 0.2 g; sodium chloride 0.2 g; beeswax 1.0 g; sodium EDTA/sodium hydroxide 2.5 g; aqua bidest. to 100 g. The oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the cream as the last cream component at 40 C.

Example 8: Formulation as a Cream

[0229] Flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 1 were incorporated in an amount of 10% (w/v) into a lamellar base cream comprising SLM 2026 (Lipoid AG, Steinhausen, Switzerland) 25 g; caprylic acid triglyceride 18 g; Simmondsia chinensis oil (jojoba oil) 6 g; pentylene glycol 3.75 g; glycerol 3 g; vitamin E acetate 1 g; panthenol 0.5 g; Tego Carbomer 140 0.2 g; sodium hydroxide (20% v/v) 0.15 g; Keltrol CG-SFT 0.1 g; aqua bidest. to 100 g. The flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the lamellar base cream as the last cream component at 40 C.

Example 9: Formulation as a Cream

[0230] Flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 1 were incorporated in an amount of 10% (w/v) into a lamellar base cream comprising SLM 2026 (Lipoid AG, Steinhausen, Switzerland) 30 g; Miglyol 812 15 g; pentylene glycol 10 g; Simmondsia chinensis oil (jojoba oil) 5 g; Butyrospermum parkii butter (shea butter) 2.0 g; squalane 1 g; Phospholipon 90H 1 g; vitamin E acetate 1 g; panthenol 0.5 g; Flowerconcentrole (Symrise, Holzminden, Germany; mixture of different blossom extracts) 1 g; aqua bidest. to 100 g. The fatty phase and the aqueous phase were first mixed separately at 60 C., with stirring. The fatty phase was homogenised for 3 minutes at 20,000 rpm, and then the aqueous phase was added to the fatty phase, with stirring, and the mixture was homogenised for 5 minutes at 20,000 rpm. After cooling, the flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone and the Flowerconcentrole were incorporated homogeneously into the cream at 40 C. and the pH was adjusted to 5.0-6.0.

Example 10: Formulation as a Cream

[0231] 18-Glycyrrhetinic acid and (Z)-guggulsterone were each incorporated in an amount of 2.5 g into a lamellar base cream comprising SLM 2026 (Lipoid AG, Steinhausen, Switzerland) 30 g; Miglyol 812 15 g; pentylene glycol 10 g; Simmondsia chinensis oil (jojoba oil) 5 g; Butyrospermum parkii butter (shea butter) 2.0 g; squalane 1 g; Phospholipon 90H 1 g; vitamin E acetate 1 g; panthenol 0.5 g; Flowerconcentrole (Symrise, Holzminden, Germany; mixture of different blossom extracts) 1 g; aqua bidest. to 100 g. The SLM 2026 base cream, the fatty phase and the aqueous phase were first mixed or heated separately at 60 C., with stirring. 18-Glycyrrhetinic acid and (Z)-guggulsterone were added to the hot fatty phase and the mixture was homogenised intensively, and then the fatty phase was added to the SLM 2026 base cream at 60 C., with stirring, and the mixture was homogenised intensively. The hot aqueous phase was then added at 60 C., with stirring, and the mixture was homogenised for 5 minutes at 20,000 rpm. After cooling, the Flowerconcentrole was incorporated homogeneously into the cream at 40 C. and the pH was adjusted to 5.0-6.0.

Example 11: Formulation as a Cream

[0232] Flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 1 were incorporated in an amount of 10% (w/v) into a cream comprising ethylhexyl stearate 10 g; Simmondsia chinensis oil (jojoba oil) 5 g; glyceryl stearate citrate 4 g; pentylene glycol 3 g; decyl oleate 2 g; vitamin E acetate 1 g; Flowerconcentrole (Symrise, Holzminden, Germany; mixture of different blossom extracts) 1 g; panthenol 0.5 g; cetearyl alcohol 0.5 g; diheptyl succinate 0.5 g; carbomer 0.5 g; aqua bidest. to 100 g. The fatty phase and the aqueous phase were first mixed separately at 60 C., with stirring. The fatty phase was homogenised for 3 minutes at 15,000 rpm, and then the aqueous phase was added to the fatty phase, with stirring, and the mixture was homogenised for 5 minutes at 20,000 rpm. After cooling, the flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone and the Flowerconcentrole were incorporated homogeneously into the cream at 40 C. and the pH was adjusted to 5.0-6.0.

Example 12: Formulation as a Cream

[0233] 18-Glycyrrhetinic acid and (Z)-guggulsterone were each incorporated in an amount of 2.5 g into a lamellar base cream comprising ethylhexyl stearate 8 g; Simmondsia chinensis oil (jojoba oil) 4 g; glyceryl stearate citrate 4 g; decyl oleate 4 g; glycerol 3 g; pentylene glycol 3 g; sucrose stearate 1 g; vitamin E acetate 1 g; Flowerconcentrole (Symrise, Holzminden, Germany; mixture of different blossom extracts) 1 g; panthenol 0.5 g; cetearyl alcohol 0.5 g; diheptyl succinate 0.4 g; carbomer 0.4 g; acrylate/C10-C30 alkyl acrylate crosspolymer 0.1 g; capryloylglycerol/sebacic acid 0.1 g; trisodium ethylenediamine 0.02 g; aqua bidest. to 100 g. The fatty phase and the aqueous phase were first mixed separately at 60 C., with stirring. The fatty phase was homogenised for 3 minutes at 15,000 rpm and then the aqueous phase was added to the fatty phase, with stirring, and the mixture was homogenised for 5 minutes at 20,000 rpm. After cooling, the Flowerconcentrole was incorporated homogeneously into the cream at 40 C. and the pH was adjusted to 5.0-6.0. Finally, homogenisation was carried out again for 3 minutes at 15,000 rpm.

Example 13: Lotion

[0234] A lotion according to the invention preferably comprises 20% (w/v) oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 2 as well as glycerol 5 g; unguentum emulsificans aquosum 15 g; propyl hydroxybenzoate 0.3 g; methyl hydroxybenzoate 0.7 g; ethanol (90% v/v) 0.9 g; aqua bidest. to 100 g. The oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the lotion as the last component at 40 C.

Example 14: Gel

[0235] To 75% (w/v) oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 2 there were added 2% propylene glycol; 0.5% sodium carbomer (PNC 400) and aqua dest. to 100%. The oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the gel as the last component at 40 C.

Example 15: Gel

[0236] 15 g of flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone from Example 1 were mixed with 75 grams of a gel base comprising 5 g of mannitol; 0.1 g of sodium edetate; 1 g of propylene glycol; 1 g of Carbopol 934 and 95 g of water. The flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the gel as the last component at 40 C.

Example 16: Gel

[0237] 18.5 g of flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone from Example 1 were processed with 1.75 g of Lipoid PG 14:1, 14:1; 3.75 g of ethanol and 76 g of aqua dest. to form a gel. The flexible soy phosphatidylcholine liposomes containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the gel at 40 C.

Example 17: Gel

[0238] 18-Glycyrrhetinic acid and (Z)-guggulsterone were each incorporated in an amount of 2.5 g into a phospholipid gel consisting of 13.5 g of Phospholipon 90G; 1.5 g of Lipoid PG 14:1, 14:1; 3.75 g of ethanol and 76.25 g of aqua dest. To that end, Phospholipon 90G was dissolved in ethanol with heating and stirring (60 C./100 rpm). 18-Glycyrrhetinic acid and (Z)-guggulsterone were melted with Lipoid PG 14:1, 14:1 at 60 C. and mixed homogeneously. The dissolved Phospholipon 90G was then added and made into a paste at 60 C. with the ingredients already present. During cooling to 45 C., aqua dest. was added stepwise and stirring was carried out slowly to form a gel. The gel was then left to swell at 45 C. before being stirred slowly for a further 5 minutes at 45 C. to give a homogeneous gel.

Example 18: Vesicles Based on a Lipidic Emulsifier from the Food Additives Group, a Monoester of a Long-Chained Fatty Acid and a Plant Oil and Comprising an Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0239] The preferred formulation comprises vesicles which comprise 8.5% (w/w) soybean oil; 3.5% (w/w) Imwitor 375; 10% (w/w) ethyl oleate; 10% (w/w) ethanol; 1.5% (w/w) diglyceryl monooleate; 0.75% (w/w) 18-glycyrrhetinic acid and 0.75% (w/w) (Z)-guggulsterone in aqua bidest. (ad 100%).

[0240] Also preferred are vesicles which comprise either 18-glycyrrhetinic acid or (Z)-guggulsterone in an amount of 1.5% (w/w):

[0241] (a) 1.5% (w/w) 18-glycyrrhetinic acid with 13.5% (w/w) sunflower seed oil; 3.5% (w/w) Imwitor 375; 5% (w/w) ethyl oleate; 10% (w/w) ethanol; 1.5% (w/w) diglyceryl monooleate in aqua bidest. (ad 100%).

[0242] (b) 1.5% (w/w) (Z)-guggulsterone with 8.5% (w/w) sunflower seed oil; 3.5% (w/w) Imwitor 375; 10% (w/w) ethyl oleate; 10% (w/w) ethanol; 1.5% (w/w) diglyceryl monooleate in aqua bidest. (ad 100%).

[0243] Both vesicle types, (a) and (b), are preferably added to the final formulation in the ratio 1:1. The plant oil (soybean or sunflower oil), Imwitor 375, ethyl oleate, diglyceryl monooleate, 18-glycyrrhetinic acid and (Z)-guggulsterone were dissolved at room temperature in ethanol, with shaking (500 rpm). Under constant conditions, aqua bidest. was then added slowly and evenly (200 l/min) to 100% (v/v), and the whole was mixed thoroughly. Finally, the dispersion was vortexed for 5 minutes, treated with ultrasound for 5 minutes (on/off interval: 10 s) and extruded through a PC filter membrane (200 nm pore size). The vesicle size was analysed by means of dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments GmbH, Herrenberg, Germany; for 5 minutes at room temperature) and was in the range 80-140 nm.

Example 19: Vesicles Based on a Lipidic Emulsifier from the Food Additives Group and a Monoester of a Long-Chained Fatty Acid and Comprising an Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0244] Preference is given to vesicles which comprise either 18-glycyrrhetinic acid or (Z)-guggulsterone in an amount of 1.5% (w/w):

[0245] (a) 1.5% (w/w) 18-glycyrrhetinic acid with 10.5% (w/w) Imwitor 375; 4.5% (w/w) ethyl oleate; 16% (w/w) ethanol in aqua bidest. (ad 100%).

[0246] (b) 1.5% (w/w) (Z)-guggulsterone with 14% (w/w) Imwitor 375; 6% (w/w) ethyl oleate; 16% (w/w) ethanol in aqua bidest. (ad 100%).

[0247] Both vesicle types, (a) and (b), are preferably added to the final formulation in the ratio 1:1. Imwitor 375, ethyl oleate, 18-glycyrrhetinic acid and (Z)-guggulsterone were dissolved at room temperature in ethanol, with shaking (500 rpm). Under constant conditions, aqua bidest. was then added slowly and evenly (200 l/min) to 100% (v/v), and the whole was mixed thoroughly. Finally, the dispersion was vortexed for 5 minutes, treated with ultrasound for 5 minutes (on/off interval: 10 s) and extruded through a PC filter membrane (200 nm pore size). The vesicle size was analysed by means of dynamic light scattering using a Zetasizer Nano ZS (Malvern Instruments GmbH, Herrenberg, Germany; for 5 minutes at room temperature) and was in the range 80-160 nm.

Example 20: Vesicles Based on Synthetic Cetyl Palmitate, a Plant Oil, a Plant Polysaccharide Copolymer and a Stearic-Acid-Based Emulsifier and Comprising an Active Ingredient Combination of 18-Glycyrrhetinic Acid and (Z)-Guggulsterone

[0248] The preferred formulation comprises vesicles of 20% (w/w) cetyl palmitate; 10% (w/w) jojoba oil; 5% (w/w) 18-glycyrrhetinic acid; 5% (w/w) (Z)-guggulsterone; 1.5% (w/w) TEGO Care PS and 0.5% (w/w) Inutec SP1 in aqua bidest. (ad 100%).

[0249] Also preferred are vesicles which comprise either 18-glycyrrhetinic acid or (Z)-guggulsterone in an amount of 5% (w/w):

[0250] (a) 5% (w/w) 18-glycyrrhetinic acid with 20% (w/w) cetyl palmitate; 10% (w/w) jojoba oil; 1.5% (w/w) TEGO Care PS and 0.5% (w/w) Inutec SP1 in aqua bidest. (ad 100%).

[0251] (b) 5% (w/w) (Z)-guggulsterone with 20% (w/w) cetyl palmitate; 10% (w/w) jojoba oil; 1.5% (w/w) TEGO Care PS and 0.5% (w/w) Inutec SP1 in aqua bidest. (ad 100%).

[0252] Both vesicle types, (a) and (b), are preferably added to the final formulation in the ratio 1:1. 18-Glycyrrhetinic acid or (Z)-guggulsterone were resuspended in jojoba oil, with stirring. The cetyl palmitate was melted at 60 C.; TEGO Care PS and the jojoba oil containing glycyrrhetinic acid and/or guggulsterone were added, with intensive stirring. Inutec SP1 was dissolved at 60 C. in purified water. At 60 C., the lipid mixture was added gradually to the Inutec SP1 solution. The dispersion was homogenised at 60 C. by means of a high-pressure homogeniser and finally cooled to room temperature.

Example 21: Formulation as a Cream Face Mask

[0253] 18-Glycyrrhetinic acid and (Z)-guggulsterone were each incorporated in an amount of 2.5 g into a lamellar base cream comprising SLM 2026 (Lipoid AG, Steinhausen, Switzerland) 86.5 g; Simmondsia chinensis oil (jojoba oil) 6 g; vitamin E acetate 1 g; panthenol 0.5 g; Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g. The ingredients were thereby incorporated homogeneously into the lamellar base cream stepwise at 40 C.

Example 22: Formulation as a Cream Face Mask

[0254] Oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 18 were incorporated in an amount of 10% (v/w) into a lamellar base cream comprising SLM 2026 (Lipoid AG, Steinhausen, Switzerland) 81.5 g; Simmondsia chinensis oil (jojoba oil) 6 g; vitamin E acetate 1 g; panthenol 0.5 g; Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g. The oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the base cream at 40 C. as the last cream component.

Example 23: Formulation as a Cream Face Mask

[0255] A cream face mask according to the invention preferably comprises 2.5 g of each of 18-glycyrrhetinic acid and (Z)-guggulsterone, which are incorporated into a base cream DAC comprising glycerol monostearate 60 4 g; cetyl alcohol 6 g; Miglyol 812 7.5 g; white petroleum jelly (vasilinum album) 25.5 g; Macrogol 20 glyceryl monostearate 7 g; propylene glycol 10 g and aqua bidest. to 100 g. The cream face mask further comprises vitamin E acetate 1 g; Simmondsia chinensis oil (jojoba oil) 5 g and Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g. The ingredients were thereby incorporated homogeneously into the base cream stepwise at 40 C.

Example 24: Formulation as a Cream Face Mask

[0256] Emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 19 were incorporated in an amount of 10% (v/w) into a base cream DAC comprising glycerol monostearate 60 4 g; cetyl alcohol 6 g; Miglyol 812 7.5 g; white petroleum jelly (vasilinum album) 25.5 g; Macrogol 20 glyceryl monostearate 7 g; propylene glycol 10 g and aqua bidest. to 100 g. The cream face mask further comprises vitamin E acetate 1 g; ethanol 5 g and Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g. The emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the base cream as the last cream component at 40 C.

Example 25: Formulation as a Cream Face Mask

[0257] Vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 20 were incorporated in an amount of 10% (v/w) into a base cream DAC comprising glycerol monostearate 60 4 g; cetyl alcohol 6 g; Miglyol 812 7.5 g; white petroleum jelly (vasilinum album) 25.5 g; Macrogol 20 glyceryl monostearate 7 g; propylene glycol 10 g and aqua bidest. to 100 g. The cream face mask further comprises vitamin E acetate 1 g; panthenol 0.5 g and Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g. The vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the cream as the last cream component at 40 C.

Example 26: Formulation as a Cream Face Mask

[0258] Oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone according to Example 18 were incorporated in an amount of 10% (v/w) into a cream comprising PEG-8 L (polyoxyethylene laurate ester) 15 g; ethyl octanoate 5 g; C12-C15 alkyl benzoate 4.5 g; glycerol (85%) 3 g; propylene glycol 3 g; vitamin E acetate 1 g; dimethicone 350 0.5 g, Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The oil emulsifier vesicles containing 18-glycyrrhetinic acid and (Z)-guggulsterone were thereby incorporated homogeneously into the formulation as the last component at 40 C.

Example 27: Formulation as a Gel Face Mask

[0259] A gel face mask according to the invention preferably comprises 2.5 g of each of 18-glycyrrhetinic acid and (Z)-guggulsterone; ethanol 5 g; mannitol 5 g; sodium edetate 1 g; propylene glycol 1 g; vitamin E acetate 1 g; Carbopol 981 0.5 g; Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The ingredients were thereby incorporated homogeneously into the formulation stepwise at 40 C.

Example 28: Formulation as a Gel Face Mask

[0260] A gel face mask according to the invention preferably comprises 2.5 g of each of 180-glycyrrhetinic acid and (Z)-guggulsterone; 2-propanol 10 g; vitamin E acetate 1 g; Carbopol 981 0.5 g; Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The ingredients were thereby incorporated homogeneously into the formulation stepwise at 40 C.

Example 29: Formulation as an Ointment Face Mask

[0261] An ointment face mask according to the invention preferably comprises 2.5 g of each of 180-glycyrrhetinic acid and (Z)-guggulsterone; ethanol 5 g; vitamin E acetate 1 g; unguentum emulsificans aquosum N SR (comprising non-ionic, emulsifying alcohols 21 g; 2-ethylhexyl laurate 10 g; glycerol (85%) 5 g; potassium sorbate 0.14 g; citrate (anhydrous) 0.07 g; aqua ad 100 g); Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The ingredients were thereby incorporated homogeneously into the formulation stepwise at 40 C.

Example 30: Formulation as an Ointment Face Mask

[0262] An ointment face mask according to the invention preferably comprises 2.5 g of each of 18-glycyrrhetinic acid and (Z)-guggulsterone; Simmondsia chinensis oil (jojoba oil) 5 g; vitamin E acetate 1 g; Linimentum aquosum N (comprising emulsifying cetyl stearyl alcohol (type A) 11.5 g; 2-ethylhexyl laurate 5 g; glycerol (85%) 2.5 g; potassium sorbate 0.07 g; citrate (anhydrous) 0.035 g; aqua to 100 g); Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The ingredients were thereby incorporated homogeneously into the formulation stepwise at 40 C.

Example 31: Formulation as a Lotion Face Mask

[0263] A lotion face mask according to the invention preferably comprises 2.5 g of each of 18-glycyrrhetinic acid and (Z)-guggulsterone; ethanol 2 g; vitamin E acetate 1 g; panthenol 0.5 g; glycerol (85%) 5 g; Pionier 1033 7 g; viscous paraffin 20 g; urea 2 g; white petroleum jelly 20 g; magnesium sulfate heptahydrate 0.5 g; methyl hydroxybenzoate 0.3 g; propyl hydroxybenzoate 0.7 g; Flowerconcentrole mix (blossom extracts; Symrise, Holzminden, Germany) 1 g and aqua bidest. to 100 g. The ingredients were thereby incorporated homogeneously into the formulation stepwise at 40 C.

[0264] The face masks of Examples 27 to 31 were further prepared using the vesicles of Examples 16, 17 and 18.

[0265] The creams, lotions and gels of Examples 4 to 17 can further be prepared using the vesicles of Examples 18, 19 and 20.

Example 32: Further Examples of Compositions of Face Masks

[0266] Ingredients composition A: [0267] Purified water [0268] Bentonite [0269] Glycerol [0270] Acacia senegal gum [0271] Xanthan gum [0272] Benzyl alcohol [0273] Ethanol [0274] Sodium dehydroacetate [0275] Simmondsia chinensis oil (jojoba oil) [0276] Sodium citrate [0277] Dehydroacetic acid [0278] Citric acid [0279] Blossom extract (fragrance) [0280] Carbomer [0281] 1,2-Hexanediol [0282] Caprylyl glycol [0283] Sodium benzoate [0284] Lactic acid [0285] Potassium sorbate [0286] Algin [0287] Panthenol [0288] Tocopheryl acetate

[0289] Ingredients composition B: [0290] Purified water [0291] Simmondsia chinensis oil (jojoba oil) [0292] Butyrospermum parkii (shea) butter extract [0293] Glycerol [0294] Glyceryl stearate [0295] Cetearyl alcohol [0296] Cera alba (beeswax) [0297] Caprylic/capric triglyceride [0298] Benzyl alcohol [0299] Sodium salicylate [0300] Blossom extract (fragrance) [0301] Levulinic acid [0302] Xanthan gum [0303] Sodium levulinate [0304] Sodium hydroxide [0305] Dehydroacetic acid [0306] Sodium benzoate [0307] Potassium sorbate [0308] Citric acid [0309] Panthenol [0310] Tocopheryl acetate

[0311] Ingredients composition C: [0312] Purified water [0313] Caprylic/capric triglyceride [0314] Hectorite [0315] Cetearyl alcohol [0316] Pentylene glycol [0317] Isopropyl isostearate [0318] Glycerol [0319] Glyceryl stearate [0320] Ceteareth-20 [0321] Panthenol [0322] Tocopherol [0323] Tocopheryl acetate [0324] Benzyl alcohol [0325] Allantoin [0326] Ceteareth-12 [0327] Cetyl palmitate [0328] Blossom extract (fragrance) [0329] Citric acid [0330] Benzoic acid [0331] Sodium hyaluronate (0.01-0.5%) [0332] Sorbic acid [0333] Benzyl alcohol

[0334] To these compositions A, B or C there are added either 18-glycyrrhetinic acid and (Z)-guggulsterone or the vesicles according to the invention.