PHENYL KETONE DERIVATIVES AS SELF-TANNING AGENTS

Abstract

The present invention relates to the use of phenyl ketone derivatives of the formula I for use as self-tanning substance or for increasing melanin synthesis, improving melanin transport and/or improving the distribution of melanin in suprabasal layers, and to preparations comprising these phenyl ketone derivatives.

Claims

1. A method of self-tanning comprising producing a self-tanning effect by applying to the skin of a host at least one compound of the formula I ##STR00007## in which R1 to R5 stand, independently of one another, for H, OH, NH.sub.2, R7, OR7 or O(C═O)R7, and R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.30-alkyl, straight-chain or branched C.sub.2- to C.sub.30-alkenyl, or a cycloalkyl or cycloalkenyl group having 5 to 8 C atoms, where the cycloalkenyl group is not an aromatic group, as self-tanning substance.

2. A method for increasing melanin synthesis, improving melanin transport and/or improving the distribution of melanin in suprabasal layers, comprising administering to a host in need thereof an effective amount of at least one compound of the formula I ##STR00008## in which R1 to R5 stand, independently of one another, for H, OH, NH.sub.2, R7, OR7 or O(C═O)R7, and R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.30-alkyl, straight-chain or branched C.sub.2- to C.sub.30-alkenyl, or a cycloalkyl or cycloalkenyl group having 5 to 8 C atoms, where the cycloalkenyl group is not an aromatic group, for increasing melanin synthesis, improving melanin transport and/or improving the distribution of melanin in suprabasal layers.

3. The method according to claim 1, wherein R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.12-alkyl, or straight-chain or branched C.sub.2- to C.sub.12-alkenyl.

4. The method according to claim 3, wherein R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.6-alkyl, or straight-chain or branched C.sub.2- to C.sub.6-alkenyl.

5. The method according to claim 4, wherein R6 and R7 stand for methyl.

6. The method according to claim 1, wherein the radicals R1 to R5 stand, independently of one another, for H, OH, NH.sub.2, methyl, OCH.sub.3 or O(C═O)CH.sub.3.

7. The method according to claim 1, wherein the radicals R2 and R4 stand for H.

8. The method according to claim 1, wherein the compounds of the formula I are compounds of the formula Ia to Ih ##STR00009##

9. A composition comprising at least one compound of the formula I ##STR00010## in which R1 to R5 stand, independently of one another, for H, OH, NH.sub.2, R7, OR7 or O(C═O)R7, and R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.30-alkyl, straight-chain or branched C.sub.2- to C.sub.30-alkenyl, or a cycloalkyl or cycloalkenyl group having 5 to 8 C atoms, where the cycloalkenyl group is not an aromatic group, and at least one further self-tanning substance, at least one UV filter, or a topical carrier.

10. (canceled)

11. (canceled)

12. (canceled)

13. A process for the preparation of a preparation according to claim 9, wherein the compound of the formula I is mixed with a vehicle which is suitable for topical applications.

14. The method according to claim 2, wherein R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.12-alkyl, or straight-chain or branched C.sub.2- to C.sub.12-alkenyl.

15. The method according to claim 2, wherein R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.1- to C.sub.6-alkyl, or straight-chain or branched C.sub.2- to C.sub.6-alkenyl.

16. The method according to claim 2, wherein R6 and R7 stand for methyl.

17. The method according to claim 2, wherein the radicals R1 to R5 stand, independently of one another, for H, OH, NH.sub.2, methyl, OCH.sub.3 or O(C═O)CH.sub.3.

18. The method according to claim 2, wherein the radicals R2 and R4 stand for H.

19. The method according to claim 2, wherein the compounds of the formula I are compounds of the formula Ia to IH ##STR00011##

20. A method of self-tanning comprising producing a self-tanning effect by applying to the skin of a host at least one compound of the formula I ##STR00012## in which R1 to R5 stand, independently of one another, for R7, OR7 or O(C═O)R7, and R6 and R7 stand, independently of one another, for straight-chain or branched C.sub.2- to C.sub.30-alkenyl, or a cycloalkyl or cycloalkenyl group having 5 to 8 C atoms, where the cycloalkenyl group is not an aromatic group, as self-tanning substance.

Description

EXAMPLES

Example 1: Performance of a B16 V Mouse Melanoma Cell Test

[0203] B16V mouse melanoma cells (manufacturer: DSMZ; Article No.: ACC370) in RPMI medium (Invitrogen, Article No.: 31870), to which 10% of FBS (foetal bovine serum; Invitrogen, Article No.: 10499044), 2 mM L-glutamine (Invitrogen, Article No: 25030) and 1 mM sodium pyruvate (Invitrogen, Article No.: 11360) had additionally been added (=modified RPMI medium), are transferred into a culture flask and incubated at 37° C. and 5% CO.sub.2 for 72 h. The medium is separated off, and the cells are washed with 10 ml of D-PBS (Dulbecco's phosphate-buffered salines; Invitrogen, Article No.: 14190) and subsequently removed by suction. 1 ml of HyQtase cell detachment solution (Hyclone, Article No.: SV30030.01) is added to the cells. The bottle is swirled a number of times, and the HyQtase cell detachment solution is subsequently removed by suction. The cells are then incubated in the incubator at 37° C. and 5% CO.sub.2 for 5 min. The cells are taken up in the modified RPMI medium (see above), and the cell count is determined. To this end, the cells are stained with Trypan Blue and counted in a Neubauer chamber. The cells are subsequently sown out again in the modified RPMI medium (see above) in a defined cell count of 80,000 cells per well (6-well clear plate, TCT, PS (Nunc)).

[0204] The cells are incubated at 37° C. and 5% CO.sub.2 for 24 h, the medium is then removed. The substance to be investigated (see table below) is subsequenly added in various concentrations.

[0205] After the final incubation period, the medium is removed by suction, and the cells are washed with 1000 μl of D-PBS (Invitrogen, Article No.: 14190). The medium is again removed by suction. 250 μl of HyQtase cell detachment solution (Hyclone, Article No.: SV30030.01) are added to the cells. The 6-well plate is swirled a number of times, and the HyQtase cell detachment solution is subsequently removed by suction. The cells are then incubated in the incubator at 37° C. and 5% CO.sub.2 for 5 min. The cells are taken up in 1.5 ml of DPBS (Invitrogen, Article No.: 14190) and transferred into a cup (SARSTEDT, Ref. 72.692.005). The cell count is subsequently determined. To this end, the cells are stained with Trypan Blue and counted in a NeuBauer chamber. The cells are then centrifuged at 3500 g for 1 min. The pellets obtained are photographed, and the supernatant is subsequently removed by suction. The pellets are dissolved in 1 ml of 1N NaOH at 80° C. for 1 h and then cooled to RT. 200 μl per cup (as quadruple determination) are subsequently pipetted into a 96-well plate (VWR, Article No.: 4100636981), and the absorption at a wavelength of 405 nm is determined (Safire, Tecan). The content of melanin can be determined in this way by means of a calibration line.

[0206] As comparison with the compounds of the formula I to be investigated, a sample with dimethyl sulfoxide (DMSO) (0.1%) as negative control and a sample with IBMX (200 μm) as positive control are each investigated in parallel.

[0207] The following tables give the results of the determination of the melanin concentration obtained for the substance dilutions indicated.

[0208] The results obtained are quoted relative to the negative control with dimethyl sulfoxide (DMSO), whose measurement value is set to 100%. IBMX serves as positive control.

TABLE-US-00001 Test 1: Melanin content in pg/B-16V cell Negative control (DMSO 0.1%) 100 IBMX (200□M) 726 Ia (50□M) 191 Ia (300□M) 429 Ia (1 mM) 438 Ib (50□M) 202 Ib (300□M) 318 Ib (1 mM) 611 Ic (50□M) 129 Ic (100□M) 144 Ic (500□M) 184

[0209] Result of Test 1:

[0210] Ia, Ib and Ic promote melanogenesis in the B16 V mouse melanoma cell test.

TABLE-US-00002 Test 2: Melanin content in pg/B-16V cell Negative control (DMSO 0.1%) 100 IBMX (200□M) 338 Id (100□M) 275 Id (500□M) 432 Ie (100□M) 104 Ie (500M) 121 Ig (100□M) 133 Ig (500□M) 209 Ih (100□M) 126 Ih (500□M) 164

[0211] Result of Test 2:

[0212] Id, Ie, Ig and Ih promote melanogenesis in the B-16V mouse melanoma cell test.

Example 2: O/W Formulation

[0213]

TABLE-US-00003 Constituents/ Source of [% by 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 (5) PROPYLPARABEN 0.05 4-hydroxybenzoate 1-(2-Methoxyphenyl) (6) 1 ethanone (Ib) B 1,2-Propanediol (5) PROPYLENE 4 GLYCOL Methyl (5) METHYLPARABEN 0.15 4-hydroxybenzoate Water, demineralised AQUA (WATER) to 100 Water, demineralised 10 Total 100.00

[0214] Preparation Process:

[0215] 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.

[0216] Sources of Supply:

[0217] (1) Sasol Germany GmbH (2) Cognis GmbH (3) BASF AG

[0218] (4) Degussa-Goldschmidt AG (5) Merck KGaA/Rona® (6) ABCR GmbH

Example 3: O/W Formulation

[0219]

TABLE-US-00004 Constituents/ Source of [% by 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 (5) PROPYLPARABEN 0.05 4-hydroxybenzoate 1-(2,4- (6) 2 Dimethoxyphenyl)- ethanone (Ie) B 1,2-Propanediol (5) PROPYLENE 4 GLYCOL Methyl (5) METHYLPARABEN 0.15 4-hydroxybenzoate Water, demineralised AQUA (WATER) to 100 Water, demineralised 10 Total 100.00

[0220] Preparation Process:

[0221] 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.

[0222] Sources of Supply:

[0223] (1) Sasol Germany GmbH (2) Cognis GmbH (3) BASF AG

[0224] (4) Degussa-Goldschmidt AG (5) Merck KGaA/Rona® (6) TCI Deutschland GmbH

Example 4: O/W Formulation

[0225]

TABLE-US-00005 Constituents/ Source of [% by 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) METHYL PARABEN 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 1-(2-Hydroxy-6- (8) 0.5 methoxyphenyl)ethanone (Id) Total 100.00

[0226] Preparation Process:

[0227] 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.

[0228] Sources of Supply:

[0229] (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 (8) Alfa Aesar GmbH

Example 5: W/O Formulation

[0230]

TABLE-US-00006 Constituents/ Source of [% by trade name supply INCI wt.] A Dow Corning 3225 C (1) CYCLOMETHICONE, 23.6 DIMETHICONE COPOLYOL Propyl 4-hydroxybenzoate (2) PROPYLPARABEN 0.05 1-(2-Hydroxyphenyl) (2) 0.5 ethanone (Ia) 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

[0231] Preparation Process:

[0232] 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.

[0233] Sources of Supply:

[0234] (1) Dow Corning (2) Merck KGaA/Rona®

Example 6: O/W Anti-Ageing Cream with UV A/B Protection

[0235]

TABLE-US-00007 Constituents/ Source of [% by trade name supply INCI wt.] A Eusolex ® 2292 (1) ETHYLHEXYL 3 METHOXY- CINNAMATE, 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 (1) PROPYLPARABEN 0.05 4-hydroxybenzoate 1-(2,4-Dimethoxy- (6) 1 phenyl)- B 1,2-Propanediol (1) PROPYLENE 3 GLYCOL Methyl (1) SODIUM 0.17 4-hydroxybenzoate METHYLPARABEN sodium salt Water, demineralised AQUA (WATER) to 100 Total 100.00

[0236] Preparation Process:

[0237] 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.

[0238] Sources of Supply:

[0239] (1) Merck KGaA/Rona®, (2) Degussa-Goldschmidt AG, (3) Cognis GmbH, (4) BASF AG, (5) Sasol Germany GmbH, (6) TCI Deutschland GmbH