J. Soc. Cosmetic Chemists, 16, 349-358 (1965) Pyridoxine- 3 , Their Use in 4-Diacylates Cosmetics and HARUYASU OHTA, M.Sc.* Presented before the Third Congress of the I.F.S.C.C., June 21-2•, 19•, New York City Synopsis--Pyridoxine-3,4-diacylates can be prepared by a new process in good yield and high purity. Data are presented to demonstrate the oil solubility and the heat and light stability of these esters. Acute and chronic toxicities of these esters indicate that they are suitable for inclusion in cosmetics. It is further shown that the esters are hydrolyzed by tissue homogenates at rates which are influenced by the acid moiety used for esterification. Finally, clinical data are presented to demonstrate the utility of pyridoxine-3,4-dipalmitate in dermal therapy. INTRODUCTION Vitamin B0 is one of the most important factors for nutrition and for health and beauty of the human skin. Hence, many attempts have been made to use vitamin B0 as a cosmetic additive. Pyridoxine hydrochloride, which is a commercially available form of vitamin B6, is not suitable for topically applied cosmetics because of its insolubility in oils and fats and its instability to heat and light. It is therefore de- sirable to prepare a heat- and light-stable, fat-soluble and percutaneously absorbable pyridoxine derivative for cosmetic use. In 1956, Sakuragi and Kummerow (1-4) first synthesized long chain fatty acid triesters of pyridoxine and confirmed that they are sources of fat-soluble, heat- and light-stable and biologically active vitamin B0 when applied to the rat. In 1961, Rocheggiani (5) reported on the cutaneous actions of * Nihon Surfactants Industries Co. Ltd., 29, 3-chome, Hasune-cho, Itabashi-ku, Tokyo, Japan. 349

35O JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS TABLE I Physical Properties of Pyridoxine-3,4-Diacylates Pyridoxine Diacylate M.P., øC Formula M.W. Dibutyrate 57-58 C16H230,•N 309.37 Dioctanoate 69-71 Cs4H39OsN 421.58 Di-iso-octanoate Liquid C24H•90•N 421.58 Dilaurate 79-80 C•H•aO.•N 533.80 Dipalmitate 88-89 C40H7•Or, N 646.01 TABLE II Solubilities of Pyridoxine-3,4-dioctanoate Solvent g./100 g. at 25øC Isopropyl myristate 2 Olive oil 1 Oleyl alcohol 3.5 Oleic acid 5 Liquid paraffin 0.07 70% ethanol 0.3 at -- 5 •-• -- 10øC 60% ethanol 0.1 at - 5 •-• - 10 C TABLE II I Solubilities of Pyridoxine-3,4-dipalmitate Solvent g./100 g. at 25øC g./100 g. at 75øC Ethanol 0.5 Isopropyl Inyristate 0.1 3 Olive oil 0.1 5 Oleyl alcohol 0.2 5.5 Oleic acid 0.1 5.5 Liquid paraffin 0.01 0.5 TABLE IV Sunlight Stability of Pyridoxine Derivatives Derivatives Irradiation Time, Transmittanee, hr. % Pyridoxinc hydrochloride Pyridoxine,B,4-dibutyrate Pyridoxine-3,4-dioctanoate 0 99 15 92 30 87 0 100 15 99 30 98 0 100 15 99.5 30 98