Clinical research summary of Créme de Vie

Tests done

The tests were undertaken at our collaborating group from University Miguel Hernandez in Elche (Spain) [Dr. Antonio Ferrer-Montiel, Centro de Biología Molecular y Celular, Universitas Miguel Hernández, 03202 Elche, Alicante, SPAIN]

Further references used

Benedetto, A.V. Environment and skin aging. Clin. Derm. 16, 129-139 (1998)
Stegman, S.J., Tromovitch, T.A., Glogau, R.G. The skin of the aging face in cosmetic dermatologic surgery. 2nd edn. St. Louis. MO: Mosby year book, 5-15 (1990)
Benedetto, A.V. The cosmetic use of Botulinum neurotoxin type A. Int. J. Derm. 38, 641-655 (1999)
Becker-Wegerich, P.M., Rauch, L. and Ruzicka, T. Botulinum toxin a: successful decollete rejuvenation. Dermatol. Surg. 28, 168-171 (2002).
Frankel, A.S. Botox for rejuvenation of the periorbital region. Facial Plast. Surg. 15, 255-262 (1999).
Johnson, E.A. Clostridial toxins as therapeutic agents: Benefits of nature´s most toxic proteins. Annu. Rev. Microbiol. 53, 551-575 (1999).
Chen, Y.A. and Scheller, R.H. SNARE-mediated membrane fusion. Nat. Rev. Mol. Cell Biol. 2, 98-106 (2001).
Gutierrez, L.M., Canaves, J., Ferrer-Montiel, A., Reig, J.A., Montal, M. and Viniegra, S. A peptide that mimics the carboxy-terminal domain of SNAP-25 blocks
Ca2+-dependent exocytosis in chromaffin cells. FEBS Lett. 372, 39-43 (1995).
Gutierrez, L.M., Viniegra, S., Rueda, J., Ferrer-Montiel, A.V., Canaves, J.M. and Montal, M. A peptide that mimics the C-terminal sequence of SNAP-25 inhibits secretory vesicle docking in chromaffin cells. J. Biol. Chem. 272, 2634-2639 (1997).
Ferrer-Montiel, A.V., Gutierrez, L.M., Apland, J.P., Canaves, J.M., Gil, A., Viniegra, S., Biser, J.A., Adler, M. And Montal, M. The 26-mer peptide released from SNAP- 25 by botulinum neurotoxin E inhibits vesicle docking. FEBS Lett. 435, 84-88 (1998).
Blanes-Mira, C., Ibáñez, C., Fernández-Ballester, G., Planells-Cases, R., Pérez-Payá, E., Ferrer-Montiel, A. (2001). Thermal stabilization of the catalytic domain of botulinum neurotoxin E by phosphorylation of a single tyrosine residue. Biochemistry 40, 2234-2242 (2001).
Ferrer-Montiel, A.V., Canaves, J.M., DasGupta, B.R., Wilson, M.C. and Montal, M. Tyrosine phosphorylation modulates the activity of clostridial neurotoxins. J. Biol. Chem. 271, 31, 18322-18325 (1996).
Hayashi, T., Yamasaki, S., Nauennburg, S., Binz, T. and Niemann, H. Disassembly of the reconstituted synaptic vesicle membrane fusion complex in vitro. EMBO J. 14, 2317-2325 (1994).

Clinical research was undertaken by the laboratory which developed the hexapeptide molecule, and skin topography analyses were performed on healthy women volunteers to measure the effectiveness of an O/W emulsion containing 10% of the hexapeptide.

Successful results confirmed the validation of the biochemical mechanism proposed.

Cosmetic benefits

It further prevents aging of the skin induced by repeated facial movements caused by excessive catecholamine release.

Effectiveness

Muscles are contracted when they receive neurotransmitters released from inside a vesicle. The SNARE (SNap REceptor) complex is essential for this neurotransmitter release at the synapses. ^{Reference 14}

It is a ternary complex formed by the proteins VAMP, Syntaxin and SNAP-25 (SyNaptosomal Associated Protein). This complex intervenes in the process of docking, fusing and exocytosis of these neurotransmitter-filled vesicles.

The hexapeptide is a mimic of the N-terminal end of SNAP-25 which competes with SNAP-25 for a position in the SNARE complex, thereby modulating its formation. If this SNARE complex is slightly destabilized, the vesicle is not able to release neurotransmitters efficiently and therefore muscle contraction is attenuated, preventing the formation of lines and wrinkles.

Underneath the clinical results of skin topography using silicon impressions taken from the lateral preorbital area in healthy women volunteers and analyzed by confocal microscopy.

The top row illustrates the use of a placebo cream, while the bottom row illustrates the use of cream using a 10% inclusion rate of the hexapeptide. The three periods from left to right illustrates the measurements taken at day 0, day 15 and day 30.