抄録
Cetraxate hydrochloride (1) (antiulcer agent) can be produced by the enzymatic debenzylation of cetraxate benzyl ester hydrochloride (2). In order to use the enzymatic method as an industrial procedure, it is essential to obtain the crystal of cetraxate (3, free compound of 1) as an intermediate from the enzymatic reaction solution. Cetraxate (3) was found to have four polymorphic forms, two anhydrides (A, B) and two hydrates (dihydrate I, II). It is very important for the practical procedure that cetraxate (3) crystal forms transform from the light crystal form (dihydrate I) to the heavy one (dihydrate II) in the enzymatic reaction solution. The transformation was strongly prevented by the cetraxate related substance, tranexamic acid-cetraxate hydrochloride condonsate (TS-1). The heavy crystal forms (dihydrate II, anhydride B) are thermodynamically more stable than the light one (dihydrate I). Crystal forms of 3 are stabilized as dihydrate II in water below 29°C and as anhydride B over 29°C.
