Patent FR-2899584-A1 (FR)
Title: Method for combating wrinkles, relaxing skin and slackening the lines of the skin involves applying adenosine derivative to the skin
Inventor: DALKO MARIA
IPC: C07D233/88
Filed: 2006-04-11
Abstract: Combating wrinkles, relaxing skin and/or slackening the lines of the skin involves applying to skin at least one adenosine derivative and its salts, optical isomers and solvates. Combating wrinkles, relaxing skin and/or slackening the lines of the skin involves applying to skin at least one adenosine derivative of formula (I) and its salts, optical isomers and solvates. R1 and R2a saturated linear 1-6C or unsaturated linear 2-6C, or saturated or unsaturated branched 3-6C hydrocarbon radical; OR1+R2isopropylidene radical; R3T1, -COR4 or an ester group resulting from biotin; R4saturated linear 1-9C or unsaturated linear 2-9C or saturated or unsaturated branched 3-9C hydrocarbon radical (optionally substituted by at least one of T2); T1a saturated linear 1-10C or unsaturated linear 2-10C or saturated or unsaturated branched 3-10C hydrocarbon radical optionally substituted by at least one of T2; T2-ORa, -NRaRb, -COORa, -CONRaRb, -CF3, -F, -OCF3, -CN or -NO2; Ra and Rbhydrogen atom or a saturated linear 1-6C or unsaturated linear 2-6C or saturated or unsaturated branched 3-6C hydrocarbon radical optionally substituted by at least one of -OZa, -NZaZb or -COOZa; Za and Zba hydrogen atom or a saturated linear 1-6C or unsaturated linear 2-6C or saturated or unsaturated branched 3-6C hydrocarbon radical. Independent claims are included for the following: (1) a composition comprising, in a medium, at least one adenosine derivative of formula (II) and its salts, optical isomers and solvates; and (2) new adenosine derivative of formula (III). R3aT1, -COR4a or an ester group resulting from biotin; R4asaturated linear 2-9C or unsaturated linear 2-9C or saturated or unsaturated branched 3-9C hydrocarbon radical optionally substituted by at least one of T2; R3bT3, -COR4b, or an ester group resulting from biotin; R4ba linear 3-9C hydrocarbon radical or a branched 3-9C hydrocarbon radical which is saturated or unsaturated, optionally substituted by at least one of T2); T3a linear 2-10C hydrocarbon radical or a branched 3-10C hydrocarbon radical which is saturated or unsaturated, optionally substituted by at least one of T2. The group R4b is other than 2-aminoethyl group. [Image] [Image] ACTIVITY : Dermatological. Two series of attached dermal equivalents comprising normal human fibroblasts were prepared: a control series without any treatment and a series treated with 2',3'-isopropylidene-5'-biotinoyladenosine (test compound) (10 mu M). The dermal equivalents were prepared as described in Asselineau et al., Exp. Cell. Res., 1985, 159, 536-539; Models in Dermatology, 1987, vol. 3, pp. 1-7. The MEM medium (1.76 times diluted) was introduced, in presence of additives (1% glutamine, 1% non-essential amino acids, 1% sodium pyruvate, 1% fungizone and 1% penicillin/streptomycin), the foetal calf serum and the 0.1N NaOH solution, into a centrifuge tube. The fibroblasts, isolated from human skin explants, were then added at the concentration of 1.5x105> cells/1 ml of culture medium. A volume/volume mixture of collagen in acetic acid at 1/1000 was then slowly added, against the wall of the tube. The combined product was then carefully mixed and distributed in the wells of a 12-well culture plate in a proportion of mixture (2 ml) per well. The final cell concentration was 3x104> cells/dermal equivalent, with a final concentration of collagen of 1 mg/ml. The culture plate was then placed in an incubator at 37[deg]C with 5% CO2. Once formed after polymerization of the collagen, the dermal equivalents were left adhered to the culture support for 3 days and then detached from the support. The evaluation of the spontaneous contraction of the treated (with the test compound) and control (without test compound) dermal equivalent was carried out by measuring their surface area at 0, 4, 8 and 24 hours, after the beginning of the spontaneous contraction. The test compound showed reduction of the contraction of the fibroblasts by 30% on average over the duration of the experiment (tested at 10 mu M), with respect to the control. The test compound thus had a significant dermo-decontracting effect which was greater than that of adenosine (reduction of 15%). MECHANISM OF ACTION : None given.