Intravenous Injections of Diamine- Acridine Sulphate. 137 



Browning and Gilmour, while investigating relationships between constitu- 

 tion and bactericidal action among basic benzol-derivatives, found that diamino- 

 acridine was more powerfully bactericidal in the presence of serum than in 

 ordinary peptone-water-agar medium. Subsequent observations by Browning, 

 Gulbransen, Kennaway and Thornton have confirmed and extended this, 

 result ; it has been found that a number of diamino-acridine derivatives with 

 substituted methyl-groups either in the amino side-chains or in the benzol 

 rings, or in both situations, e.g., the dye acridine yellow, are all enhanced in 

 their bactericidal action by serum. This is likewise the case with Benda's 

 compound, 3 : 6-diamino-lO-methyl-acridinium chloride. 



In the presence of serum tliis group of substances constitutes the most 

 potent bactericidal agents known, and the property of being enhanced in this 

 activity by serum, so far as we are aware, is shared by no other type of 

 chemical compound which has been investigated. On account of this 

 property, together with the fact that they are comparatively non-toxic to 

 mammalian tissues, and devoid of inhibitory eftect on phagocytosis, diamino- 

 acridine salts (sulphate and chloride) and diamiuo-methyl-acridinium chloride 

 have been recommended as therapeutic substances for local application in 

 the treatment of bacterial infection in wounds. Their bactericidal action is 

 slowly progressive and the maximum effect is attained only after a con- 

 siderable time, thus concentrations of these substances which at first merely 

 inhibit proliferation of the organisms viltimately prove lethal ; in this respect 

 they differ from such substances as phenol, mercuric chloride, and sodium- 

 toluene-para-sulphochloramide. Thus, if mixtures of serum with varying 

 propox'tions of any of the latter compounds are inoculated with a suspen- 

 sion of a culture of living micro-organisms, such as Staphylococcus aureus or 

 B. coli, and are placed in the incubator at 37° C, it is found on making 

 subcultures at intervals, that if a given concentration of antiseptic has not 

 proved lethal in two hours, its presence has little effect in preventing the 

 occurrence of active multiplication of the organisms subsequently. 



On the other hand, with the acridine compounds the effect in two hours 

 is very slightly greater than with mercuric chloride, but the concentration 

 which proves lethal in 24 hours is only a tenth to a twentieth of the lethal 

 concentration of mercuric chloride. Thus, it was found that a concentration 

 of 1 : 10,000 of mercuric chloride killed these organisms in serum in two 

 liours, but with a concentration of 1 : 20,000 the bacteria were still alive 

 after 24 hours and had multiplied actively. Witli diamino-methyl-acridinium 

 chloride, however, the lethal concentration after two hours was 1 : 20,000, 

 and after 24 hours a strength of 1 : 100,000 and 1 : 200,000 had killed 

 B. coli and Staphylocomis mtrcus respectively ; diamino-acridine sulphate is 



