Attention has been paid to the thiocarbanilide derivative and the authors synthesized some new compounds of thiocarbanilides for experimental studies on tuberculosis and leprosy. The series of newly synthesized chemical compounds of thiocarbanilides were studied for comparision with the already known antimycobacterial agents; INH, PAS, Streptomycin and D. D. S. The strains of Mycobacterium tubercubsis (H37 Rv, Ravenel, and B. C. G.) and Mycobacterium phlei were used for the in vitro experiments. In the in vivo experiments, the strain of Mycobacterium tuberculosis var. bovis (Ravenel) was employed. The strain of Mycobacterium leprae murium (Hawaiian strain) was used for the murine leprosy experiments. The experimental animals for the in vivo tests were white mice (CFW strain) and these were extensively employed in tuberculosis and leprosy as well. Sixteen cases of Various types of human leprosy, were treated with one of the newly synthesized thiocarbanilides (L-4). Among the newly synthesized chemical compounds of thiocarbanilides studied for their antituberculous and antimurine leprosy activity in vitro and in vivo experiments, two compounds were shown to be suppressive agents for those infections without significant toxicity. These two compounds were named tentatively as L-1 and L-4. 1) LD50 of L-1 was 1,054 mg/kg and that of L-4 was 1,028 mg/kg, while the LD50 of INH was 650 mg/kg and PAS was 4,000mg/kg orally in the experimental animals. 2) L-1 and L-4 showed remarkable suppressive activity in vitro using solid media with 100r/ml. concentration. These data were parallel to 1r/ml. of INH and 50r/ml. of PAS. The inferiority of L-1 and L-4 to INH and PAS in vitro studies might have been due to the water insolubility of these compounds while INH and PAS were readily soluble in water. 3) In vivo experiments with L-1 showed a much-more superior antituberculous effect than was found with INH and PAS. 4) A method of grading the bacterial count in a homogenized tissue suspension of visceral organs (lungs, liver, spleen and kidneys) using the simple technique of the Gaffky scale was accurate and time saving technique in screening the results of the chemotherapeutic agents in tuberculosis. 5) Among the newly synthesized compounds L-4 showed the most remarkable suppressive effect on murine leprosy. The suppressive results were similar to those of INH. 6) The method of measuring the size and the weight of leproma at the inoculated site was simple and is an adequate screening test for chemotherapeutic effect in murine leprosy. 7) In the trials with human leprosy 16 cases of various types, using L-4, the effectiveness in clinical as well as in bacteriological improvement was remarkable. a) After L-4 treatment decrease in bactriologica1 indices and remarkable clinical improvement after a relative1y short period of treatment were observed. b) L-4, up to the maximum daily dose of 500 mg, can be safely administered orally to the patients without any significant side reactions. c) L-4 could be used with remarkable clinical improvement for the patients in lepra reactions.
Adult ; Animals ; Comparative Study ; Erythema Nodosum/drug therapy ; Female ; Human ; Leprosy/*drug therapy ; Male ; Mice ; Thiourea/*therapeutic use

A total of 62 leprosy patients, 47 lepromatous type, 9 tuberculoid, 5 borderline group and 1 indeterminate group, have been treated with a synthesized thiocarbanilide L-4, and the effectiveness of L-4 administration in the treatment of leprosy is evaluated on the basis of clinical and bacteriological improvements. The results are summarized and conc1uded as follows; 1. L-4, contained in gelatin capsule, can be safely administered orally to the patients through slow induction, from initial dosages of 50 mg to 100 mg dai1y to the therapeutic maintenance levels of 200 mg to 300 mg daily, for a period of time. 2. L-4 administration has brought apparent and remarkable improvement in clinical symptoms of the patients after a relatively short period of medication compared with that of DDS administration. 3. Changes of SFG values caused by L-4 administration were much speedier than, (or, at least, equivalent to) the effect caused by DDS. The changes of SFG values, in general, synchronized fairly well with clinical improvement of the patients. 4. Lepromatous cases with leprosy reaction or sulfone allergy responded well to L-4 medication with remarkable clinical improvement, and prolonged administration of L-4 did not provoke such a precipitating action to leprosy reaction as did DDS.
Adolescent ; Adult ; Anilides/chemical synthesis ; Anilides/therapeutic use* ; Anti-Infective Agents/chemical synthesis ; Anti-Infective Agents/therapeutic use* ; Child ; Female ; Human ; Leprosy/drug therapy* ; Male ; Middle Age ; Sulfur*