DEVELOPMENT OF POLYETHOXYLATED RETINAMIDE AS AN ANTI-AGING AGENT

  • Published : 1999.12.31

Abstract

A novel retinol derivative, polyethoxylated retinamide(Medimin A) was synthesized, as an anti-aging agent. Collagen synthesis, skin permeation, stability, and toxicity of Medimin A were evaluated and compared with those of retinol and retinyl palmitate. In vitro collagen synthesis was evaluated by quantitative assay of $[^3H]-proline$ incorporation into collagenase sensitive protein in fibroblast cultures. For in vitro skin permeation experiments, Franz diffusion cells(effective diffusion area: 1,766 $cm^2$) and the excised skin of female hairless mouse aged 8 weeks were used, The stabilities of retinoids were evaluated at two different temperature($25^{\circ}C\;and\;40^{\circ}C$) and under UV in solubilized state and in O/W emulsion. To estimate the safety, acute oral toxicity, acute dermal toxicity, primary skin irritation, acute eye irritation and human patch test were performed. The effect of Medimin A on collagen synthesis was similar to that of retinol. The skin permeability of Medimin A was higher than those of retinol and retinyl palmitate. The Medimin A was more stable than retinol and retinyl palmitate. Medimin A was nontoxic in various toxicological tests. These results suggest that Medimin A would be a good anti-aging agent for enhancing bioavailability and stability.

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References

  1. J. Invest Dermatol. v.81 Kubilus, J.
  2. Jpn. v.20 Koizumi, Y.;Fragrance, J.
  3. J. Clin. Invest. v.75 Oikarinen, H.;Oikarinen, A.(et al.)
  4. Biochem. Biophys. Res. Commun. v.114 Beach, R.;Kenny, C.
  5. Biochem. Biophys. Acta. v.889 Kenny, M.;Shin, L.(et al.)
  6. Develop. Biol. v.118 Benya, P.;Padilla, S.
  7. Skin Pharmacol. v.6(suppl. 1) Pfahl, M.
  8. J. Invest Dermatol. v.103 Saurat, J.H.;Didierijean, L.(et al.)
  9. Skin Pharmacol. v.6(suppl. 1) Gendimenico, G.J.;Mezick, J.A.
  10. J. Am. Acad. Dermatol. Kligman, A.M.;Grave, G.L.(et al.)
  11. JAMA v.259 Weiss, K.S.;Ellis, C.N.(et al.)
  12. v.127 Bhawan, J.;Gonzalez-Serva, A.(et al.)
  13. The New England J. of Med. v.6 Rafal, F.S.;Griffiths, C.E.M.(et al.)
  14. Methods in Enzymology v.190 Packer, L.(et al.)
  15. Vitamins v.15 Kwasaki, C.;Hida, M.
  16. Vitamins v.18 Tabata, T.
  17. Vitamins v.28 Hayashi, S.;Nishii, Y.
  18. II farmaco v.47 Semenzato, A.;Secchreri, M.(et al.)
  19. J. Appl. Cosmetol. v.11 Erling, Thom
  20. Br. J. Dermatol. v.90 Sperman, R.I.C.;Jarrett, A.
  21. J. Med. Chem. v.24 Cecchi, R.;Rusconi, L.(et al.)
  22. Anal Biochem. v.96 Webster, David F.;Harvey, Wilson
  23. 20th IFSCC Congress Evaluation of in vitro skin permeation of UV filters Song, Y.S.(et al.)