[Pharmaceutical and pharmacological development of antitumor prostaglandins]

Antitumor Prostaglandins such as delta 12PGJ2 and delta 7PGA1 possess a cross-conjugated dienone unit and exhibit unique antitumor effect. Lipid microshere (w/o type emulsion) was selected as pharmaceutical formulation because of physicochemical properties of prostaglandin. 13,14-Dihydro-15-deoxy-delta 7-PGA1 methyl ester (TEI-9826) were selected as a candidate for clinical trial. In a rat and mouse serum in vitro, TEI-9826 rapidly metabolized to 13,14-dihydro-15-deoxy-delta 7-PGA1 (TOK-4528), but TOK-4528 is stable as well as delta 12PGJ2. Lipid microshere containing TEI-9826 at the content of 5 mg/ml exhibited administration route and schedule dependent antitumor effect in vivo using Colon 26 bearing mouse model, which suggested that duration of serum concentration was important for antitumor effect. One of the antitumor mechanism of antitumor PG might be an induction of the cyclin-dependent kinase inhibitor p21. PPAR gamma also might be important. New type homogenizer, high pressure jet flow type homogenizer was developed in the study of antitumor prostaglandin.