Antibacterial activity of 21 kinds of penicillin derivatives was tested in vitro and reported in the previous report (part 1) of this study. In this report, experiments were made on the toxicity in mice, titration of the blood level and protective effect in experimentally infected mice.
Following results were obtained.
LD50 of the 21 kinds of penicillin derivatives in mice varied from 1.5 mg to 4.5 mg. When inoculated subcutaneously. Aminoacidester-Penicillin was rather lower in toxicity and prccain-Pc and p-aminobenzaldehyde thiosemicarbazone-Pc were relatively stronger. When injected subcutaneously, the toxicity of penicillin salt seemed to be different according to the base reacted to penicillin. But the toxicity was very low when administered orally, and all the mice survived, even though a dose of 75 mg was given. Employing the mice infected with Str, equi, 5 kinds of penicillin derivatives were tested of their protectivity. When a dose of 30 units was used, 3-6/10 of the mice died, but when a dose of 90 units was used, only 0-2/10 died.
The death rate seemed to be reduced by the increase in the dose given. Further more it was found that d.1-p-nitrophenyl-2-amino-l.3-propanediol-Pc, 1-leucineethylester-Pc and p-aminoben-zaldehyde thiosemicarbazone-Pc seemed to be less toxic than procain-Pc and that are quite promis-sing agents in the therapeutic field.
Two kinds of pyrimidine-Pc and 3 kinds of aminoacidester-Pc were as effective as procain-Pc and penicillin G-Na in experimentally produced pneumococcal infection, but it seemed advisable to give a dose over 50 or 100 units for better results.
The therapeutic effect of pyrimidine-Pc in Type 1 pneumococcal infection in mice seemed to be larger, when given in combination with sulfamine.
In the case of mousetyphoid, all animals died. Judging from the mean survival days of experimental animals, however, the survival period of animals administered of d.1-p-nitrophenyl-2-amino-l.3-propanediol-Pc seemed slightly longer than those of administered of 2-amino-4-methyl-6-methoxypyrimidine-Pc.
Thus, it is believed that a number of newly prepared penicillin derivatives are as effective as procain-Pc or penicillin G-Na.
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