A study on the chemotherapeutic agent against
C. diphtheriae was carried out already by Behring (1, 2) side by side with his study in the serotherapy. Boer (3), Eeiler (4-6), Burkard and Dorn (7), Langer (8), N euf eld, Schieman and Baumgarten (9), Reinhardt (10), Ritter and Schenkel (11), Brunner and Gonzenbach (12), Browning and Gulbransen (13), Goldschmidt (14), Braun and Goldschmidt (15), Shibanuma and Hata (16, 17) followed after him in the study of the same field.
In the early stages they investigated about inorganic substances but later chiefly about organic substances and especially about acridine derivatives. The strong bacteriostatic action of acridine compounds in vitro attracted their interest and they have succeeded also in saving animals from experimental diphtheria infection. But no clinician has intended as yet to treat the infection of human beings with acridine compounds, because of the uncertainty of effect. Injection of antitoxin serum is the most trustworthy-treatment; the serum is capable not only to neutralize the toxin, but to inhibit the growth of bacilli and cures the disease in its earlier stage with promptitude. But on the other hand the serum is somewhat inconvenient to treat with and troublesome in its production. The apparition of such a compound, as not only capable of inhibiting the growth of bacilli, but also to destruct or to neutralize toxin in vivo, if possible, might be desirable. Of course we have had comprehensive studies on the detoxication. of diphtheria toxin, while those works were to gain an effective anatoxin for the use in preventing the disease. Formol, ketene, vanilline, adrenaline, sodium salicylate, urea, quinine salt, gluthathion, soap, ricinoleic sodium salt, colloidal manganese, colloidal iron, various anorganic salts, ascorbic acid, hormones, enzymes etc, were namely the detoxicating agents in this sense, but none of these seems to be practically useful as therapeuticum, because they have no strong detoxifying ability in vivo.
Meanwhile penicillin appeared and a ray of hope has been thrown for a new treatment of diphtheria, yet so far we do not know about its final success.
On this occasion a number of compounds were investigated by us (18-21), in the bacteriostatic and bactericidal action against
C. diphtheriae and among 120 chemicals, inclusive of 15 phenothiazine, 5 phenoxazine, 13 quinoline, 4 acridine, 31 diphenylsulf one, . 17 diphenylsulfide, 5 diphenyldisulfide, 15 diphenylether, 9 tetronic acid derivatives, citrinin, kojic acid, usnic acid and 3 others, usnic acid was found to be the only substance, that can not only save animals from experimantal diphtheria infection (22), but also detoxify the toxin.
The usnic acid, used in these studies, was extracted from
Usnea longissima. Fp 203°C [a]
13D= +491.8° (in chloroform) .
The acid has recently been reported to have strong bacteriostatic effect on the growth of the tubercle bacillus and the
Staphylococcus aureus (23-25), but no one has ever reported in details about its effectiveness in diphtheria infection. The experiment here reported was designed in order to observe the effect of usnic acid in experimental diphtheria infection and its action on the toxin.
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