2-pyrones

Abstract

The present invention relates to the use of compounds of the formula (I) for the care, preservation or improvement of the general condition or appearance of the skin or hair, and to preparations comprising compounds of the formula (I).

Claims

1. A cosmetic or pharmaceutical composition comprising at least one compound of the formula (I) ##STR00020## where R1 stands for a straight-chain or branched C.sub.1- to C.sub.20-alkyl group, R2 stands for H or straight-chain or branched C.sub.1- to C.sub.20-alkyl group, R4 stands for H, straight-chain or branched C.sub.1- to C.sub.20-alkyl group or straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds, R3 stands for a radical selected from H, straight-chain or branched C.sub.2- to C.sub.20-alkyl group, straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds, where the alkenyl group may also be substituted by one or more saturated or unsaturated C.sub.3- to C.sub.12-cycloalkyl groups, straight-chain or branched C.sub.2- to C.sub.20-alkynyl group having one or more triple bonds, saturated or partially unsaturated non-aromatic C.sub.3- to C.sub.12-cycloalkyl group, where the rings may in each case also be bridged by (CH.sub.2).sub.n groups where n=1 to 3, an acyl radical of the formula C(O)R6, R6 stands for straight-chain or branched C.sub.1- to C.sub.20-alkyl group, a radical of the formula (II) ##STR00021## in which X stands for straight-chain or branched C.sub.1- to C.sub.6-alkylene or straight-chain or branched C.sub.2- to C.sub.6-alkenylene and the radicals R5 are selected, independently of one another, from H, OH, straight-chain or branched C.sub.1- to C.sub.6-alkyl or straight-chain or branched O(C.sub.1- to C.sub.6-alkyl), at least one vehicle which is suitable for a topical application, and a further anti-ageing or anti-cellulite active compound; with the proviso that R4 is a straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds or R3 is a straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds, where the alkenyl group may also be substituted by one or more saturated or unsaturated C.sub.3- to C.sub.12-cycloalkyl groups, straight-chain or branched C.sub.2- to C.sub.20-alkynyl group having one or more triple bonds, saturated or partially unsaturated non-aromatic C.sub.3- to C.sub.12-cycloalkyl group, where the rings may in each case also be bridged by (CH.sub.2).sub.n groups where n=1 to 3, or an acyl radical of the formula C(O)R6.

2. A composition according to claim 1, wherein the at least one compound of the formula (I) is present in an amount of 0.01 to 20% by weight.

3. A process for the preparation of a composition according to claim 1, which comprises mixing the compound of the formula (I) with a vehicle which is suitable for a topical application.

4. A composition according to claim 1, wherein, in formula (I), R1 stands for a straight-chain or branched C.sub.1- to C.sub.6-alkyl group.

5. A composition according to claim 1, wherein, in formula (I), R2 stands for H or a straight-chain or branched C.sub.1- to C.sub.6-alkyl group.

6. A composition according to claim 1, wherein, in formula (I), R4 stands for H or a straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds.

7. A composition according to claim 1, wherein, in formula (I), R3 stands for a radical selected from H, straight-chain or branched C.sub.2- to C.sub.20-alkyl group, straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds, where the alkenyl group may also be substituted by one or more saturated or partially unsaturated non-aromatic cyclohexyl groups, or an acyl radical of the formula C(O)R6.

8. A composition according to claim 1, wherein, in formula (I), the radicals R5 are selected, independently of one another, from H, OH or straight-chain or branched O(C.sub.1- to C.sub.6-alkyl).

9. A composition according to claim 1, wherein, the compound of the formula (I) is selected from the compounds of formulae (Id) to (Ii): ##STR00022## ##STR00023##

10. A composition according to claim 1, wherein, in formula (I), the radical R3 stands for a radical selected from straight-chain or branched C.sub.2- to C.sub.20-alkenyl group having one or more double bonds, where the alkenyl group may also be substituted by one or more saturated or unsaturated C.sub.3- to C.sub.12-cycloalkyl groups, straight-chain or branched C.sub.2- to C.sub.20-alkynyl group having one or more triple bonds, saturated or partially unsaturated non-aromatic C.sub.3- to C.sub.12-cycloalkyl group, where the rings may in each case also be bridged by (CH.sub.2).sub.n groups where n=1 to 3, or an acyl radical of the formula C(O)R6.

11. A compound of one of the formula (Id) to (Ii) ##STR00024## ##STR00025##

12. A composition according to claim 2, wherein, the compound of the formula (I) is selected from the compounds of the formula (Id) to (Ii): ##STR00026## ##STR00027##

Description

EXAMPLES

Example 1: 6-Methyl-4-tetradecyloxy-2-pyrone (Ic)

(1) ##STR00013##

(2) 2.50 g (19.8 mmol) of 4-hydroxy-6-methyl-2-pyrone (Ia) and 3.30 ml (23.8 mmol) of triethylamine are initially introduced in 12.5 ml of acetonitrile. The mixture is heated to 82 C., and 6.50 ml (23.8 mmol) of 1-bromotetradecane is added at this temperature. The milky-yellow solution is then boiled under reflux for 16 h. After 4 h, a white solid starts to precipitate out. The testing for complete reaction conversion was carried out by TLC analysis (dichloromethane/methanol 9:1). Cooling of the suspension to RT causes so much solid to precipitate out that the mixture becomes solid. The mixture is diluted with acetonitrile in order to make it stirrable, the solid is filtered off with suction via a suction filter, rinsed with acetonitrile and dried in vacuo at RT. The solid obtained is recrystallised from ethanol.

(3) Yield: 2.20 g=34.4% of theory

(4) Colour: white

(5) Empirical formula: C.sub.20H.sub.34O.sub.3

(6) Molecular weight: 322.5 g/mol

(7) Analysis:

(8) MS (EI): m/e (relative intensity, %)=322 ([M+] 14)

(9) .sup.1H-NMR (CDCl.sub.3, 400 MHz): =5.78-5.76 (m, 1H, H-1), 5.37 (d, 1H, J=2.1 Hz, H-5), 3.92 (t, 2H, J=6.5 Hz, H-7), 2.20 (s, 3H, H-3), 1.80-1.71 (m, 2H, H-8), 1.50-1.17 (m, 22H, H-9 to H-19), 0.88 (t, 3H, J=6.7 Hz, H-20)

Example 2: 4-Hexadecanoyloxy-6-methyl-2-pyrone (Id)

(10) ##STR00014##

(11) 5.00 g (39.6 mmol) of 4-hydroxy-6-methyl-2-pyrone (Ia) and 4.40 g (39.6 mmol) of potassium tert-butoxide are initially introduced in 100 ml of N,N-dimethylformamide. 13.2 ml (43.6 mmol) of palmitoyl chloride is then added dropwise to the dark-yellow suspension at RT, and the solution, which is now pale yellow, is stirred at RT for 16 h. A reaction check using TLC (eluent: dichloromethane/methanol 9:1) shows complete conversion. Water is added to the reaction mixture, during which solid precipitates out. The mixture is stirred for a further 30 min, the solid is then filtered off with suction via a suction filter, rinsed with water and dried in vacuo at 40 C. The purification is carried out by crystallisation from ethanol.

(12) Yield: 4.00 g=27.7% of theory

(13) Colour: yellowish

(14) Empirical formula: C.sub.22H.sub.36O.sub.4

(15) Molecular weight: 364.5 g/mol

(16) Analysis:

(17) MS (EI): m/e (relative intensity, %)=364 ([M+] 3)

(18) .sup.1H-NMR (CDCl.sub.3, 400 MHz): =6.04-6.02 (m, 1H, H-1), 5.96-5.94 (m, 1H, H-5), 2.52 (t, 2H, J=7.5 Hz, H-8), 2.26 (s, 3H, H-3), 1.70 (quint, 2H, J=7.4 Hz, H-9), 1.43-1.19 (m, 24H, H-10 to H-21), 0.88 (t, 3H, J=6.7 Hz, H-22).

Example 3: 4-((E)-3,7-Dimethylocta-2,6-dienyloxy)-6-methyl-2-pyrone (Ie)

(19) ##STR00015##

(20) 5.00 g (39.6 mmol) of 4-hydroxy-6-methyl-2-pyrone and 6.60 g (43.6 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) are initially introduced in 80.0 ml of acetonitrile and heated to 80 C. 7.90 ml (39.6 mmol) of (E)-1-bromo-3,7-dimethylocta-2,6-diene is then carefully added and heated under reflux for 40 h. The testing for complete reaction conversion is carried out by TLC analysis (toluene/ethyl acetate 4:1). The reaction mixture is evaporated to dryness and purified by chromatography with toluene/ethyl acetate 9:1.

(21) Yield: 1.0 g=9.6% of theory

(22) Colour: colourless

(23) Empirical formula: C.sub.16H.sub.22O.sub.3

(24) Molecular weight: 262.3 g/mol

(25) Analysis:

(26) MS (EI): m/e (relative intensity, %)=262 ([M+] 4)

(27) .sup.1H-NMR (CDCl.sub.3, 500 MHz): =5.79-5.75 (m, 1H, H-1), 5.41-5.37 (m, 2H, H-5+H-8), 5.12-5.05 (m, 1H, H-13), 4.51 (d, 2H, J=6.8 Hz, H-7), 2.19 (s, 3H, H-3), 2.14-2.03 (m, 4H, H-11+H-12), [1.71 (s, 3H), 1.68 (s, 3H), 1.60 (s, 3H)] H-10+H-15+H-16.

(28) .sup.13C-NMR (DMSO, 300 MHz): =170.5 (C-4), 165.2 (C-2 or C-6), 160.4 (C-2 or C-6), 143.5 (C-9), 132.1 (C-14), 123.3 (C-13), 117.2 (C-8), 100.7 (C-1), 88.0 (C-5), 65.7 (C-7), 39.5 (C-11), 26.2 (C-12), 25.7 (C-16), 19.8 (C-3), 17.7 (C-15), 16.7 (C-10).

Example 4: 3-((E)-3,7-Dimethylocta-2,6-dienyl)-4-hydroxy-6-methyl-2-pyrone (Ii)

(29) ##STR00016##

(30) 5.00 g (39.6 mmol) of 4-hydroxy-6-methyl-2-pyrone and 6.60 g (43.6 mmol) of DBU are initially introduced in 80.0 ml of acetonitrile and heated to 80 C. 7.90 ml (39.6 mmol) of (E)-1-bromo-3,7-dimethylocta-2,6-diene is then carefully added and heated under reflux for 40 h. The conversion is checked using TLC (eluent: toluene/ethyl acetate 4:1). The reaction mixture is evaporated to dryness, purified by chromatography with toluene/ethyl acetate 4:1, then with ethyl acetate/ethanol 1:1.

(31) Yield: 1.60 g=15.4% of theory

(32) Colour: yellow

(33) Empirical formula: C.sub.16H.sub.22O.sub.3

(34) Molecular weight: 262.3 g/mol

(35) Analysis:

(36) MS (EI): m/e (relative intensity, %)=262 ([M+] 23)

(37) .sup.1H-NMR (DMSO, 500 MHz): =14.49 (s, 1H, H-7), 5.98 (s, 1H, H-1), 5.13-5.07 (m, 1H, H-9), 5.06-5.00 (m, 1H, H-14), 2.95 (d, 2H, J=7.1 Hz, H-8), 2.11 (s, 3H, H-3), 1.99 (q, 2H, J=7.0 Hz, H-13), 1.89 (t, 2H, J=7.0 Hz, H-12), [1.65 (s, 3H), 1.59 (s, 3H), 1.52 (s, 3H)] H-11+H-16+H-17.

(38) .sup.13C-NMR (DMSO, 300 MHz): =164.6 (C-4+C-6), 159.7 (C-2), 134.4 (C-10), 130.6 (C-15), 124.1 (C-14), 121.6 (C-9), 100.6 (C-5), 99.8 (C-1), 38.7 (C-12), 26.1 (C-13), 25.4 (C-17), 21.6 (C-8), 19.2 (C-3), 17.5 (C-16), 15.9 (C-11).

Example 5: 4-Ethanoyloxy-6-methyl-2-pyrone

(39) ##STR00017##

(40) 2.00 g (15.9 mmol) of 4-hydroxy-6-methyl-2-pyrone and 1.50 ml (15.9 mmol) of acetic anhydride are suspended in 16.0 ml of toluene, and 16.0 l (0.30 mmol) of sulfuric acid are added. The suspension is stirred at RT for 16 h, the conversion is checked using TLC (eluent: ethyl acetate/heptane 2:1). The solid (corresponds to the starting material) is filtered off with suction, the mother liquor is evaporated in a rotary evaporator. The residue obtained is purified by column chromatography with ethyl acetate/heptane 2:3.

(41) Yield: 1.20 g=45.0% of theory

(42) Colour: yellowish

(43) Empirical formula: C.sub.8H.sub.8O.sub.4

(44) Molecular weight: 168.1 g/mol

(45) Analysis:

(46) MS (EI): m/e (relative intensity, %)=168 ([M+] 28)

(47) .sup.1H-NMR (DMSO, 400 MHz): =6.30-6.28 (m, 1H, H-1), 6.05-6.02 (m, 1H, H-5), 2.27 (s, 3H, H-3), 2.25-2.23 (m, 3H, H-8).

(48) .sup.13C-NMR (DMSO, 300 MHz): =167.2 (C-4), 163.7 (C-2 or C-6), 163.5 (C-2 or C-6), 162.8 (C-7), 101.5 (C-5), 100.6 (C-1), 20.9 (C-8), 19.4 (C-3).

Example 6: 4-(2-Ethylhexanoyloxy)-6-methyl-2-pyrone

(49) ##STR00018##

(50) 2.50 g (19.8 mmol) of 4-hydroxy-6-methyl-2-pyrone and 2.20 g (19.8 mmol) of potassium tert-butoxide are initially introduced in 50.0 ml of N,N-dimethylformamide. 3.50 g (21.8 mmol) of 2-ethylhexanoyl chloride is then added dropwise to the dark-yellow suspension at RT. The reaction mixture is stirred at RT for 16 h. A reaction check using TLC (eluent: dichloromethane/methanol 9:1) shows complete conversion. Water and tert-butyl methyl ether (MtB ether) are added to the reaction mixture. The phases are separated, the aqueous phase is extracted with MtB ether, the combined organic phases were washed with water, dried over sodium sulfate, filtered and evaporated in a rotary evaporator. The residue is purified by column chromatography with ethyl acetate/heptane 2:1.

(51) Yield: 4.10 g=82.0% of theory

(52) Colour: yellowish

(53) Empirical formula: C.sub.14H.sub.20O.sub.4

(54) Molecular weight: 252.3 g/mol

(55) Analysis:

(56) MS (EI): m/e (relative intensity, %)=252 ([M+] 7)

(57) .sup.1H-NMR (DMSO, 400 MHz): =6.27-6.24 (m, 1H, H-1), 6.03-6.01 (m, 1H H-5), 2.56-2.47 (m, 1H, H-8), 2.26 (s, 3H, H-3), 1.72-1.41 (m, 4H, H-9+H-13), 1.39-1.18 (m, 4H, H-10+H-11), 0.97-0.81 (m, 6H, H-12+H-14) .sup.13C-NMR (DMSO, 300 MHz): =172.5 (C-4), 163.7+163.3+163.2 (C-2+C-6+C-7), 101.4 (C-1), 101.0 (C-5), 47.4 (C-8), 31.3 (C-9), 29.5 (C-10), 25.2 (C-13), 22.5 (C-11), 20.0 (C-3), 13.8 (C-12), 11.7 (C-14).

Example 7: 4-(1-Ethylpentyloxy)-6-methyl-2-pyrone (Ij)

(58) ##STR00019##

(59) 2.50 g (19.8 mmol) of 4-hydroxy-6-methyl-2-pyrone and 3.30 ml (23.8 mmol) of triethylamine are initially introduced in 12.5 ml of acetonitrile. The mixture is heated to 82 C., and 3.90 g (21.8 mmol) of 3-bromoheptane was added at this temperature. The orange-yellow solution is then boiled under reflux for 16 h. The testing for complete reaction conversion is carried out by TLC analysis (dichloromethane/methanol 9:1). The reaction mixture is evaporated to dryness in a rotary evaporator, the subsequent purification is carried out by column chromatography with ethyl acetate/heptane 2:1.

(60) Yield: 1.40 g=31.5% of theory

(61) Colour: yellowish

(62) Empirical formula: C.sub.13H.sub.20O.sub.3

(63) Molecular weight: 224.3 g/mol

(64) Analysis:

(65) MS (EI): m/e (relative intensity, %)=224 ([M+] 15)

(66) .sup.1H-NMR (DMSO, 400 MHz): =5.90-5.87 (m, 1H, H-1), 5.52 (d, 1H, J=2.2 Hz, H-5), 4.42 (quint, 1H, J=5.9 Hz, H-7), 2.16 (s, 3H, H-3), 1.69-1.52 (m, 4H, H-8+H-12), 1.36-1.19 (m, 4H, H-9+H-10), 0.93-0.83 (m, 6H, H-11+H-13).

(67) .sup.13C-NMR (DMSO, 300 MHz): =170.2 (C-4), 165.3 (C-2 or C-6), 162.0 (C-2 or C-6), 101.0 (C-1), 87.9 (C-5), 80.3 (C-7), 32.5 (C-8), 27.3 (C-9), 26.1 (C-12), 22.8 (C-10), 19.7 (C-3), 13.9 (C-11), 9.3 (C-13).

Example 8: cDNA Array

(68) The assay is carried out using primary epidermal keratinocytes. After incubation at 37 C. and in a 5% CO.sub.2 atmosphere for 48 hours, the culture medium (DPBS and HyQtase cell detachment solution) is removed, and the test substances 4-hydroxy-6-methyl-2-pyrone Ia (40 M) and 3-((E)-3,7-dimethylocta-2,6-dienyl)-4-hydroxy-6-methyl-2-pyrone Ii (50 M) in assay medium (keratinocytes basal medium M2 and supplement mix) are added. All-trans retinoic acid is used as positive control. The cells are then cultured at 37 C. and under 5% CO.sub.2 for 24 hours.

(69) The mRNA is isolated using the RNEASY Minikit test kit from Qiagen in accordance with the instruction manual. 1 g of the RNA is then in each case converted into cDNA with the aid of the Firsts Strand cDNA synthesis kit from Roche. The 20 l of cDNA obtained are diluted 1/10, and 110 l of TaqMan Universal PCR Master Mix are in each case added to 110 l of the cDNA samples. 100 l are pipetted per slot into the Custom TaqMan array cards. The cards are sealed, centrifuged and then measured using the TaqMan 7900HT. The values obtained are standardised. Values less than or equal to 1.5 indicate moderate to strong downregulation of the expression of the genes investigated.

(70) The influences of hydroxy-6-methyl-2-pyrone Ia (40 M) and 3-((E)-3,7-dimethylocta-2,6-dienyl)-4-hydroxy-6-methyl-2-pyrone Ii (50 M) on the gene expression of the cell envelope proteins calmodulin-like protein (CALML5), filaggrin (FLG), involucrin (IVL), loricrin (LOR), repetin (RPTN), calgranulin A and B (S100A8, S100A9) and transglutaminase 1 (TGM1) are shown in Table 1.

(71) TABLE-US-00001 TABLE 1 Application CALML5 FLG IVL LOR all-trans retinoic acid 2.93 3.20 4.05 7.01 (5 M) Ia (40 M) 3.14 1.01 1.76 4.56 Ii (50 M) 2.58 4.67 3.82 1.59 RPTN S100A8 S100A9 TGM1 all-trans retinoic acid 2.56 3.26 3.49 3.56 (5 M) Ia(40 M) 3.33 1.74 2.18 1.26 Ii (50 M) 1.57 2.93 1.48 1.56

(72) For hydroxy-6-methyl-2-pyrone Ia (40 M), the table shows an inhibiting action of mRNA production for the cornified envelope, apart from filaggrin. Compound Ii also exhibits uniform downregulation of gene expression, apart from repetin. The comparison all-trans retinoic acid exhibits a homogeneous picture of the reduction of mRNA for all cell envelope proteins. The downregulation of this gene family is a typical feature of substances which have an antidifferentiating action.

(73) A second group of genes (Table 2) considered encodes for proteins which correlate with cell-cell connections. Corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoplakin (DSP) and desmocollin 3 (DSC3) are tested, the associated regulation factors are shown in Table 2. The expression of all genes is downregulated by Ia and Ii. The downregulation of this protein family is known for retinoids.

(74) TABLE-US-00002 TABLE 2 Application CDSN DSC3 DSG1 DSP all-trans retinoic acid (M) 2.37 1.23 9.22 1.56 4-Hydroxy-6-methyl-2-pyrone 2.14 1.69 1.39 1.40 Ia (40 M) 3-((E)-3,7-Dimethylocta-2,6- 13.20 1.14 8.20 1.53 dienyl)-4-hydroxy-6-methyl-2- pyrone Ii (50 M)

(75) The results of the cDNA array show a similar expression pattern to retinoic acid.

Example 9: Ex-Vivo Study

(76) Histological explants having an average diameter of 10 mm from the lower abdomen tissue of a 45-year-old European woman are prepared. The pieces of tissue are stored in BEM medium in a moist, 5% CO.sub.2 atmosphere at 37 C. The tissue is divided into 3 batches of 6 explants each.

Test Substances and Sampling

(77) TABLE-US-00003 Application Sampling K Day 8 V Mygliol/ethanol (80/20) Day 8 P 4-Hydroxy-6-methyl-2- Day 8 pyrone Ia (1% in Mygliol/ethanol 80/20)

(78) Batch K represents the negative control. Only the vehicle is applied to batch V. Batch P is treated with 4-hydroxy-6-methyl-2-pyrone Ia (1% in Mygliol/ethanol 80/20). 30 l of the 1% substance solutions in Myliol/ethanol (80/20) are applied using a round filter paper and allowed to act for 2 hours. Applications are carried out on day 0, 1, 4, 6 and 7.

(79) On the 8th day, 3 pieces of tissue from each batch are fixed in Bouin solution. After fixing for 48 hours, the samples are dehydrated by means of Leica TP 1020 and soaked in paraffin. Tissue sections with a thickness of 5 m are produced from the paraffin blocks using a microtome and mounted on Superfrost specimen slides. The microscopic investigation is carried out using a Leica Orthoplan microscope after the tissue sections mounted on specimen slides have been stained with Masson-Goldner trichrome stain. In order to be able to assess the effect of the substances, the thickness of the epidermis or the change thereof is measured.

(80) Results: on day 0, the skin explants employed are investigated morphologically, and the test substances are then applied topically for the first time. The general morphology of the skin sections shows a moderately thick stratum corneum.

(81) After 8 days, the morphology of the untreated skin (batch K) is virtually unchanged.

(82) The skin tissue exposed to the vehicle (batch V) exhibits only a slight change in the stratum granulosum and a reduction in the parakeratosis which is present in untreated skin.

(83) Treatment with substance Ia (batch P) induces moderate growth of the epidermis. Compared with the vehicle, a 10% thicker epidermis is measured on the 8th day after exposure to compound Ia. The collagen network in the dermis along the dermo-epidermal junction zone becomes denser.

Example 10: Lipolysis

(84) The study is carried out using normal human adipocytes originating from the lower abdomen biopsy of a 31-year-old woman. The hypodermis is isolated from the biopsy and incubated at 37 C. for 30 minutes with collagenase solution. The separated adipocytes are washed and diluted with assay medium (MEM without Phenol Red, penicillin 25 UI/ml/streptomycin 25 l/ml, L-glutamine 2 mM, bovine serum albumin (BSA), fatty acid-free: 0.5% (p/v)).

(85) The test solutions or the caffeine reference are added to the cell suspensions, and the mixtures are incubated at 37 C. and in a 5% CO.sub.2 atmosphere for 2 hours. The pyrones tested and concentrations are indicated in the table.

(86) After this time, the unesterified fatty acids liberated from the samples are quantified.

(87) The measurement is carried out using a Wako NEFA-C test kit in accordance with the instruction manual.

Test Substances and Concentrations for Lipolysis

(88) TABLE-US-00004 Test substance Test concentrations Caffeine 1 mM 4-Methoxy-6-methyl-2- 0.25 mM; 0.5 mM; 1 mM pyrone Ib and 2 mM 3-((E)-3,7-Dimethyl-octa- 0.25 mM; 0.5 mM; 1 mM 2,6-dienyl)-4-hydroxy-6- and 2 mM methyl-2-pyrone Ii 4-(1-Ethylpentyloxy)-6- 0.25 mM; 0.5 mM; 1 mM methyl-2-pyrone Ij and 2 mM

(89) Results: compound Ib promotes triacylglycerin degradation (82% stimulation significant at 2 mM). Compound Ij exhibits a similar course (57% stimulation significant at 2 mM). Both substances increase the lipolytic activity as a function of concentration.

(90) The results for compound Ii (67% (at 2 mM) or 60% (at 1 mM)) indicate that compound Ii is able to counter the breakdown of subcutaneous fatty tissue which begins during skin ageing (filling effect for antiageing).

Example 11: O/W formulation

(91) TABLE-US-00005 Source of Constituents/trade name supply INCI [wt-%] A Marlipal 1618/11 (1) CETEARETH-11 3 Lanette O (2) CETEARYLALCOHOL 7 Luvitol EHO (3) CETEARYLOCTANOATE 5 Tegosoft TN (4) C12-15 2.5 ALKYLBENZOATE Miglyol 812 N (1) CAPRYLIC/CAPRIC 2.5 TRIGLYCERIDE Propyl 4- (5) PROPYLPARABEN 0.05 hydroxybenzoate 0.05 3-((E)-3,7-Dimethylocta- 2,6-dienyl)-4-hydroxy-6- methyl-2-pyrone B 1,2-Propanediol (5) PROPYLENE 4 GLYCOL Methyl 4- (5) METHYLPARABEN 0.15 hydroxybenzoate AQUA (WATER) to 100 Water, demineralised Water, demineralised 10 Total 100.00
Preparation Process:

(92) Firstly, phase A is warmed to 75 C. and phase B to 80 C. Phase B is then slowly added to phase A with stirring and stirred until a homogeneous mixture forms.

(93) Sources of Supply:

(94) (1) Sasol Germany GmbH (2) Cognis GmbH (3) BASF AG (4) Degussa-Goldschmidt AG (5) Merck KGaA/Rona

Example 12: O/WW Formulation

(95) TABLE-US-00006 Source of Constituents/trade name supply INCI [wt-%] A Marlipal 1618/11 (1) CETEARETH-11 3 Lanette O (2) CETEARYLALCOHOL 7 Luvitol EHO (3) CETEARYLOCTANOATE 5 Tegosoft TN (4) C12-15 2.5 ALKYLBENZOATE Miglyol 812 N (1) CAPRYLIC/CAPRIC 2.5 TRIGLYCERIDE Propyl 4- (5) PROPYLPARABEN 0.05 hydroxybenzoate Retinol (3) (2E,4E,6E,8E)-3,7- 0.04 Dimethyl-9-(2,6,6- trimethylcyclohex-1- enyl)nona-2,4,6,8-tetraer 1-ol 3-((E)-3,7-Dimethylocta- 0.1 2,6-dienyl)-4-hydroxy-6- methyl-2-pyrone (Ii) B 1,2-Propanediol (5) PROPYLENE 4 GLYCOL Methyl 4- (5) METHYLPARABEN 0.15 hydroxybenzoate AQUA (WATER) to 100 Water, demineralised Water, demineralised 10 Total 100.00
Preparation Process:

(96) Firstly, phase A is warmed to 75 C. and phase B to 80 C. Phase B is then slowly added to phase A with stirring and stirred until a homogeneous mixture forms.

(97) Sources of supply:

(98) (1) Sasol Germany GmbH (2) Cognis GmbH (3) BASF AG (4) Degussa-Goldschmidt AG (5) Merck KGaA/Rona

Example 13: O/W Formulation

(99) TABLE-US-00007 Source of Constituents/trade name supply INCI [wt-%] A Tego Care 150 (1) GLYCERYL 8 STEARATE, STEARETH-25, CETETH-20, STEARYL ALCOHOL Lanette O (2) CETEARYL 1.5 ALCOHOL Luvitol EHO (3) CETEARYL 5 OCTANOATE Miglyol 812 N (4) CAPRYLIC/CAPRIC 5 TRIGLYCERIDE Paraffin liquid (5) PARAFFINUM 3 LIQUIDUM (MINERAL OIL) AbilWax 2434 (1) STEAROXY 1.6 DIMETHICONE Dow Corning 200 Fluid (6) DIMETHICONE 0.5 (350 cs) Propyl 4-hydroxybenzoate (5) PROPYLLPARABEN 0.05 B 1,2-Propanediol (5) PROPYLENE 3 GLYCOL Methyl 4-hydroxybenzoate (5) METHYLPARABEN 0.15 Water, demineralised AQUA (WATER) to 100 C Probiol L 05018 (Empty (7) AQUA, ALCOHOL 5 liposomes) DENAT, LECITHIN, GLYCERINE, DISODIUM PHOSPHATE Water, demineralised AQUA (WATER) 10.00 4-Hydroxy-6-methyl-2- 1 pyrone Total 100.00
Preparation Process:

(100) Firstly, phases A and B are warmed to 80 C. Phase B is then slowly added to phase A with stirring and homogenised. The mixture is then cooled, and phase C is added at 40 C.

(101) Sources of Supply:

(102) (1) Degussa-Goldschmidt AG, (2) Cognis GmbH, (3) BASF AG, (4) Sasol Germany GmbH, (5) Merck KGaA/Rona, (6) Dow Corning, (7) Kuhs GmbH & Co. KG

Example 14: W/O formulation

(103) TABLE-US-00008 Source of Constituents/trade name supply INCI [wt-%] A Dow Corning 3225 C (1) CYCLOMETHICONE, 23.6 DIMETHICONE COPOLYOL Propyl 4-hydroxybenzoate (2) PROPYLPARABEN 0.05 4-Hydroxy-6-methyl-2- 1 pyrone B Methyl 4-hydroxybenzoate (2) METHYLPARABEN 0.15 1,2-Propanediol (2) PROPYLENE 35.9 GLYCOL Water, demineralised AQUA (WATER) to 100 Total 100.00
Preparation Process:

(104) Firstly, phase B is dissolved and then added to phase A. The pH is adjusted to the value pH=6.0 using sodium hydroxide solution or citric acid.

(105) Sources of Supply:

(106) (1) Dow Corning (2) Merck KGaA/Rona

Example 15: O/W Antiageing Cream with UV A/B Protection

(107) TABLE-US-00009 Source of Constituents/trade name supply INCI [wt-%] A Eusolex 2292 (1) ETHYLHEXYL 3 METHOXYCINNAMATE, BHT Eusolex 4360 (1) BENZOPHENONE-3 0.5 Tego Care 150 (2) GLYCERYL 8 STEARATE, STEARETH-25, CETETH-20, STEARYL ALCOHOL Lanette O (3) CETEARYL 1.5 ALCOHOL Luvitol EHO (4) CETEARYL 5 OCTANOATE Miglyol 812 N (5) CAPRYLIC/CAPRIC 5 TRIGLYCERIDE Paraffin liquid (1) PARAFFINUM 3 LIQUIDUM (MINERAL OIL) Abil-Wax 2434 (2) STEAROXY 1.6 DIMETHICONE Dow Corning 200 Fluid (6) DIMETHICONE 0.5 (350 cs) Propyl 4- (1) PROPYLPARABEN 0.05 hydroxybenzoate 3-((E)-3,7-Dimethylocta- 1 2,6-dienyl)-4-hydroxy-6- methyl-2-pyrone (Ii) B 1,2-Propanediol (1) PROPYLENE 3 GLYCOL Methyl 4- (1) SODIUM 0.17 hydroxybenzoate METHYLPARABEN sodium salt Water, demineralised AQUA (WATER) to 100 Total 100.00
Preparation Process:

(108) Firstly, phases A and B are mixed separately and warmed to 80 C. Phase B is then slowly added to phase A with stirring. The mixture is homogenised cooled to room temperature.

(109) Sources of Supply:

(110) (1) Merck KGaA/Rona, (2) Degussa-Goldschmidt AG, (3) Cognis GmbH, (4) BASF AG, (5) Sasol Germany GmbH, (6)

Example 16: Anticellulite Cream

(111) TABLE-US-00010 Constituents % A Cetyl alcohol 2 Glyceryl Stearate 5 Caprylic/Capric Triglyceride 8 Isopropyl Palmitate 9 4-methoxy-6-methyl-2-pyrone 1 B Glycerin 3 Preservatives (Germaben II) 0.8 Water, demineralised to 100
Preparation Process:

(112) Firstly, phase B is dissolved and then added to phase A. The pH is adjusted to the value pH=6.0 using sodium hydroxide solution or citric acid.

(113) Use:

(114) Apply to the skin twice daily with vigorous massaging; carry out circular and up and down movements in the process. The treatment can be carried out both on thighs and also buttocks and stomach.