<原著>4-4' Diisoamyloxythiocarbanilide の試験管内抗結核菌作用に関する研究

Abstract

The antituberculous activity of 4, 4'-diisoamyloxythiocarbanilide (DAT) was studied in vitro, including the problem of cross resistance among DAT, thioacetazone and ethionamide. The results obtained were as follows : 1. The minimum inhibitory concentration of DAT against H37Rv strain was 3.13mcg. per ml. in Tween-albumin liquid medium and 12.5-25mcg. per ml. in Kirchner's liquid medium with 10% bovine serum, on 1% Ogawa's egg solid medium and in silicone-coated slide culture. 2. The tuberculostatic activity was lower in of a medium of pH6.5 than in one of pH5.5 or 7.5, and was less influenced by the size of the inoculum. 3. The medium-replacing culture method proved that DAT was unstable in Kirchner's medium and its biological activity decreased rapidly. 4. The tuberculostatic effect was examined in Kirchner's liquid medium with 10% bovine serum against 50 strains of Mycobacterium tuberculosis isolated from untreated patients. Of these, 20% were inhibited by 6.25 mcg. per ml., 50% by 12.5 mcg. per ml. and 30% by 25mcg. or more per ml. 5. Resistance to DAT developed very slowly and occurred only twice even after 5 transfers. 6. The development of kanamycin resistance was retarded by combining it with DAT under the conditions of this experiment. 7. The cross resistance berween DAT and other antituberculous drugs was studied in laboratory resistant strains derived from a sensitive strain of H37Rv. There was no cross resistance between DAT and streptomycin, kanamycin, viomycin, isoniazid, or p-aminosalicylic acid. H37Rv strain resistant to thioacetazone was completely resistant to DAT and vice versa. A slight incomplete cross resistance between DAT and ethionamide was observed. On the other hand, H37Rv strain resistant to ethionamide was slightly resistant to thioacetazone although one resistant to thioacetazone remained sensitive to ethionamide.