[A 50-year history of new drugs in Japan: the developments of antileprosy drugs and their epidemiological aspects].

The developments of antileprosy drugs and their influences on the epidemiological aspects of Hansen's disease (leprosy) in Japan are investigated. 1. Hydnocarpus oil (Daifushi-Yu) products were the only useful drugs for the treatment of Hansen's disease (leprosy) in Japan from the early 1900's to just after the World War II. In those days leprosy was considered to be incurable malady. 2. The chemotherapy of leprosy, progressing from 1943 in the United States, was introduced to Japan in 1948. Promin(R) (sulfoxone sodium) for injection in 1948 and Diasone(R), and Promizole(R) for oral use in 1949 were available for the treatment of leprosy patients in the National Hansen's Disease Sanatorium in Japan. Because DDS (dapsone, diaphenylsulfone) was proved to be the main ingredient of sulfone drugs, since 1958 it has been the drug of choice for all forms of leprosy. Monotherapy with DDS has continued for more than 30 years, and sulfone-resistant bacillus has appeared occasionally. 3. Clofazimine (a new type of chemotherapeutic drug) and rifampicin (an antibiotic for tuberculosis) was added to therapy treatment for leprosy in 1996. In 1983, WHO recommended multidrug therapy (MDT) to prevent resistance to sulfones. The Japanese Leprosy Association published "Guidlines" for the Treatment of Hansen's Disease in Japan" in 2000, which proposes a multidrug therapy with rifampicin, DDS, and clofazimine for a 6-month or 2-year treatment. 4. The number of leprosy patients has slowly decreased since the application of chemotherapy with sulfone drugs, and newly infected patients in Japan have decreased to less than 10 per million persons (Figs. 1 & 2). Therefore the "Leprosy Prevention Law" (1953), which compels the controlled isolation of patients, was abolished in 1996. Effective chemotherapy with sulfone and other drugs has changed incurable leprosy to a curable infective disease.