854 CHEMOTHERAPY 



tissues of the infected animals, and its great superiority over all other 

 substances that possess spirillicidal properties. 



Clinical evidence in the treatment of human syphilis supported the 

 experimental findings. On account of the disadvantages of salvarsan, 

 due to its insolubility and the necessity for using the hydrochlorid, and 

 also in an effort still further to lessen its toxicity, Ehrlich conducted 

 further researches to discover a neutral salt that would be more soluble 

 and less toxic. As a result of these efforts neosalvarsan, or "914," has 

 been produced. This number is significant of the number of experiments 

 performed since the discovery of "592" and "606." 



Properties of Salvarsan. Salvarsan is the dihydrochlorid of dioxy- 

 diamidoarsenobenzol, and occurs as a yellow, crystalline, hygroscopic 

 powder, very unstable in air, and easily oxidized to poisonous com- 

 pounds. It is marketed commercially put up in small sealed vacuum 

 tubes. It contains 31.57 per cent, of arsenic, is readily soluble in water, 

 particularly in hot water, and yields a solution having an acid reaction. 

 If the acidity is neutralized by the addition of caustic soda solution, 

 the unsoluble base (dioxydiamidoarsenobenzol) is precipitated. If only 

 half of this amount of alkali is added, then the monohydrochlorid of 

 dioxydiamidoarsenobenzol is formed. If, in addition to the amount of 

 caustic soda necessary to precipitate the base, a further quantity of al- 

 kali is added, the hydrogen atoms of the phenol hydroxyls become re- 

 placed by Na and the compound goes into solution as the disodium 

 salt of dioxydiamidoarsenobenzol: 



As As As As 



AS\ S\ <^ 



NH 2 C1H NH 2 = |NH 2 



OH OH ONa ONa 



Dihydrochlorid (salvarsan) Disodium salt (alkaline solution) 



Test-tube experiments showed less spirillicidal power of the drug 

 than is demonstrated in the living animal. The following table shows 

 the toxicity of the preparation (Ehrlich and Hata) : 



