SOLUBLE BROMINATED SALICYLANILIDES 347 for several days in a clear bottle. The preshave lotion and the shampoo retained their original appearances even after remaining in direct sunlight for a month. All of the preparations retained their original color when stored in amber bottles. CONCLUSIONS AND DISCUSSION Unsuccessful attempts were made to increase the solubility of ET-394 by various physical methods. It was found possible, however, to increase its solubility in aqueous media by formation of its alkali metal salts without any hydrolysis of the amide linkage. When the potassium, sodium, and ammonium salts are dissolved in distilled water or ethanol (50%) and exposed to sunlight, they developed a brown color with precipitation after short periods of time. Amber bottles, which have been used in the past to prevent light degradation, proved useful in preventing chemical decomposition of the salt solutions. Solutions of potassium, sodium, and ammonium ET-394 (0.5%) in ethanol (50%) were tested for antibacterial activity when fresh and after six months' storage in amber bottles. At the end of the six month period the solutions retained their original antibacterial activities, clearness and colorless appearance. Thus, it seems that solubility is not a primary factor in the mechanism of action of the brominated salicylani- lides. I.R. studies of the various salts indicated further that only slight changes in the internal bonding of the compounds took place during salt formation. Because of its high solubility, good antibacterial action and ease of manufacture, potassium ET-394 (0.2%) was eventually tested in each of three formulations, an aftershave lotion, a preshave lotion, and a shampoo. After a few days a brown color was detectable only in the aftershave lotion in the clear glass bottle, while the remaining prepara- tions appeared unchanged. Antibacterial testing, however, produced no evidence to support loss of activity by degradation since the activity of the brown solution was equal to that of the clear ones. It is concluded that the salts of brominated salicylanilides have solubility properties which can be utilized in preparations in which other antibacterial agents would be insoluble or possibly inactivated by components of the system. (Received September 9, 1964)

348 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Acknowledgment The authors are grateful to The Dow Chemical Company and Stecker Chemicals, Inc., for their financial assistance and for the chemicals they so generously contributed. REFERENCES (1) Taborsky, R. G., and Starkey, R. J., J. Pharm. Sci., 51, 1152 (1962). (2) Vinson, L. J., Ambye, E. L., Schneider, W. C., Bennett, A. G., and Travers, J. J., Ibid., 50,827 (1961). (3) Lemaire, H., Schramm, C. H., and Cahn, A., Ibid., 50,831 (1961). (4) Schuler, L., U.S. Pat. 2,802,029 (1957). (5) Stecker, H., U.S. Pat. 2,906,711 (1959). (6) Stecker, H. C., and Faust, R. E., J. Soc. Cosmetic Chemists, I 1,347 (1960). (7) Mattson, G. C., Belgium Pat. 582,183 (1959). (8) Russell, K:. L., and Hoch, S., J. Soc. Cosmetic Chemists, 16,169 (1965). (9) Geiger, W., Med. Chem., Abhandl. Med.-Chem. Forschungstaetten Farbenfabriken Bayer A. G., 7,568 (1963).