尿路結石症における Sodium Pentosan Polysulphate (SPP) 療法の研究

Abstract

Concerning with the inhibitory activity of sodium pentosan polysulphate (SPP) on calcium oxalate stone formation, the following three experiments were carried out. 1) The inhibitory activities for calcium oxalate crystal formation, aggregation and growth in vitro, 2) the effects on the deposition of calcium oxalate crystals in rats treated with ethylene glycol, and 3) the effects of oral administration to human subjects on the metastable limit of urinary calcium oxalate and on the inhibitory activity of the urine for calcium oxalate crystal growth. The results were as follows: 1. The degree of the calcium oxalate crystal formation measured by an aggregometer was decreased by addition of more than 1 mM of SPP. 2. The inhibitory activity of SPP on calcium oxalate crystal aggregation was measured using a Coulter Counter. The aggregation was inhibited at a low concentration of SPP (0.02 microM). 3. Calcium oxalate crystal growth was measured using a seeded crystal method with [14C] oxalic acid. SPP inhibited the crystal growth proportionally to the concentration of SPP (0.1 microM-100 microM). 4. Renal tubular deposition of calcium oxalate crystals was marked in rats that orally received ethylene glycol (0.4%), which was expected to be suppressed by intramuscular administration of SPP (30 mg/kg/day or 60 mg/kg/day). 5. Oral administration of SPP (500 mg/day) to five healthy male subjects for five days resulted a tendency to increase of the metastable limit of the urinary calcium oxalate as measurement by an aggregometer, but the inhibitory activity of the urine for calcium oxalate crystal growth, which was measured by seeded crystal method with [14C] oxalic acid, showed no variable changes.