As reported by Takeuchi, et al.¹⁾, kanamycin was adsorbed by phosphoprotein fraction of egg yolk or a similar fraction of ground brain and eluted by acid aqueous methanol or acid water. This modus of adsorption and elution suggests that the mechanism of this adsorption on high molecular acid substances in the tissue such as phosphoproteins is similar to that on cation exchange resin. Kanamycin which has basic groups²⁾ can be adsorbed on high molecular acid substances in the brain by ion exchange mechanism. On the other hand, when water-soluble basic antibiotcs are injected to animals, toxic reaction first appears in eighth nerve system or kidney. Therefore, the authors considered that toxicity of water-soluble basic antibiotics to nerve system or kidney would be related with their basic properties. Then, if a derivative which has not the basic property and retains antimicrobial effect is found, it must have lower toxicity to the nerve system or kidney. From this view point, derivatives of kanamycin were studied.

Kanamycin-di-N-methanesulfonate and kanamycin-tetra- N-methane-sulfonate prepared by S. Umezawa, one of the present authors, were found to retain the bacteriostatic activity. The former had the amphoteric property and the latter the acid. The former had more than 20 times lower toxicity than kanamycin sulfate and the latter about 10 times lower toxicity. Therefore, a similar derivative of fradiomycin (neomycin) was prepared and was found to reduce the toxicity very markedly.

This paper describes bacteriostatic effects, acute toxicities, blood levels and therapeutic effects on bacterial infections of the derivatives above described.