Pyronaridine tetraphosphate (1) is a well-known antimalarial drug. However, it required a carefully optimized production process for the manufacture of pyronaridine tetraphosphate. Each step of its manufacturing process was reinvestigated. For the cyclization of 4-chloro-2-(6-methoxy-pyridin-3-yl-amino)-benzoic acid 6 to 7,10-dichloro-2-methoxybenzo[b]-1,5-naphthyridine 5, an improved process was developed to eliminated critical process impurity (BIA). By the redesign of the formation of triphosphate salt, the purity as API grade was increased. Thus, a robust manufacturing process with an acceptable process performance has been developed to produce high quality pyronaridine tetraphosphate.

In a river bend the water surface is inclined by the centrifugal force toward the transverse section. If channel slope and flow rate increase, the gradient is rising generally. There are lots of the flood damage at the bends of mountain river because the flood water levels have exceeded frequently the levee levels which are added a free board to the design flood water level. Therefore the superelevation should be considered in designing the mountainous river bend. In present study it was proposed to estimate the superelevation at the bend of mountain river and the superelevation coefficient defined from multiplying the sub-factors. The values of the influence factors for the superelevation coefficient were suggested from analyzing the superelevation measured at the bends in Yangyangnamdae river and the hydraulic experiments in gravel-bed channel with a 90°bend. The applicability of these methods to estimate the superelevation at the bends in mountain river was verified by the superelevation measured at the bend in Naerin river.