AS-3201 is the compound of the following formula. Said compound is described in Example 22 of Japanese Patent No. 2516147 (U.S. Pat. No. 5,258,382), Reference Example 12 of JP-A-6-192222 (Chem. Abstr., 122, 9860 (1995)), and Experiment of JP-A-8-176105 (Chem. Abstr., 125, 221569 (1996)), and its potent aldose reductase inhibitory activities are disclosed therein.

Example 28 of Japanese Patent No. 2516147 (USP 5258382) describes a method for preparing specific tablets of AS-3201. That is, it is described therein that AS-3201 (1 g), corn starch (25 g), lactose (58 g), crystalline cellulose (11 g), hydroxypropylcellulose (3 g), light anhydrous silicic acid (1 g) and magnesium stearate (1 g) are blended, granulated and made into 1,000 tablets each weighing 100 mg by a conventional method.
During the studies on methods for preparing AS-3201-containing pharmaceutical compositions having an excellent bioavailability, the present inventors have found that the water-solubility of said substance is extremely low in the range of low pH to the extent of several μg/ml, and therefore, the plasma concentration of AS-3201 varies widely among the individuals to be administered.
Under such circumstances, the present inventors have further intensively studied, and have found that by using micronized AS-3201 in a composition, the dissolution characteristics of said substance from the composition are remarkably improved, and as a result, an AS-3201-containing fast-dissolving pharmaceutical composition having a good bioavailability can be obtained, and finally have accomplished the present invention.
USPTO Backgrounds
USPTO Backgrounds