Creating Innovative Drugs to Save People from Disease in the Post-war Period—the Story of the First Domestically Produced Drug for Infectious Diseases and the Development of Groundbreaking Tuberculosis Drugs
Having sustained severe damage in 1945, Daiichi Pharmaceutical Co., Ltd. (Daiichi), one of Daiichi Sankyo's predecessors, was determined to contribute to people's health after the war and promptly regained its footing to establish a production system and launch drugs for treating infectious diseases. The company also produced a drug that would become a beacon for treating tuberculosis (TB), for which patients traditionally had to wait to recover on their own.
Following severe damage, goes on to develop Japan's first new drug with fortitude and perseverance.
Daiichi’s head office in Nihonbashi was virtually destroyed in 1945, and three of its four Kanto plants were also severely damaged. Newly based at the Yanagishima plant, which miraculously escaped damage, the company resumed pharmaceutical production the following year in 1946. Despite raw material shortages and price hikes, the company initially produced the industrial chemicals, hydrosulfite and lactic acid, and the antibacterial ointment, Therapol. The company then launched Adistin, a cardiotonic that was the first new drug after the war to be perfected by growing its key ingredient, the plant digitalis, in-house. In 1947, the company launched several pharmaceuticals, including sulfaguanidine, a sulfa drug effective against dysentery and enteritis.
Subsequently, in 1948, the company launched Theradiazine, a sulfadiazine for treating infectious diseases, which was manufactured at the Yanagishima plant. Sulfadiazine was already known for its superior medicinal properties because it had been used by injured U.S. soldiers during the war. This drug was produced using proprietary technology and marketed as Japan’s first domestic pharmaceutical product.
Theradiazine became widely adopted as it had fewer side effects with no lack of efficacy compared with conventional sulfadiazine. As Daiichi had already launched its first domestically produced sulfa drug, Therapol, in 1937, the addition of Theradiazine established the company as a leading manufacturer of sulfa drugs.
Pasnal, a ray of hope for patients with TB in Japan
During this period, Daiichi also entered the new field of TB treatment. At the time, TB treatment in Japan was limited to waiting for illness to run its course spontaneously, and alternative treatment was not available. In contrast, two types of treatment, streptomycin (SM) and para-aminosalicylic acid (PAS), had been introduced in Europe and the United States. Daiichi set out to develop a TB treatment comparable with these agents.
Around 1947, the company first introduced Tuberflavin, a treatment for tuberculous abscesses. Although it was not a definitive drug for TB, it attracted attention as the only treatment available for tuberculous abscesses. Further research led to the development of a unique synthesis of PAS, which was introduced in 1950 as Pasnal, a chemotherapeutic agent for TB. Pasnal was highly regarded as a pioneering chemotherapeutic agent for TB until the advent of hydrazide, which is still in use today.
Succeeds in producing Iscotin, a highly effective treatment for TB, in a short period
Daiichi's development of TB chemotherapeutic agents did not end there. In 1952, when a new TB chemotherapeutic agent, isonicotinic acid hydrazide (INAH), was manufactured by way of trial in the United States, it was reported in the press as a miracle drug for TB with remarkable clinical efficacy, causing a great sensation in Japan.
Daiichi took up the challenge of trial production and succeeded in synthesizing a few grams of INAH within a mere 10 days of the press report. Small vials of approximately 10g were prepared, and basic experiments and clinical trials were initiated in hospitals, TB sanatoriums, and university laboratories in various parts of Japan. The results showed that it had fewer side effects and was more effective than the more expensive SM and PAS, which required larger doses. Orders started pouring in even before the product was launched. Employees at the Yanagishima plant rushed to set up a mass production system, and a few months later, Iscotin was launched.
Competition was certain to intensify as 45 pharmaceutical companies had received approval to produce similar therapeutic agents. However, by being one of the first to provide hospitals and other institutions with a sample of Iscotin, Daiichi demonstrated its high quality and gained a solid foothold as a groundbreaking chemotherapeutic agent for TB.
In the bleak post-war period, Daiichi steadfastly rose to the challenge of new drug development and developed innovative medicines that gave hope to patients suffering from intractable diseases. This passion remains deeply rooted in Daiichi Sankyo today.
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