Basic Studies on N"-Ursodeoxycholyldiethylenetriamine-N, N, N'-triacetic Acid for the Dissolution of Calcified Gallstones

• Published in: Biological & pharmaceutical bulletin Vol. 21; no. 6; pp. 551 - 557
• Main Authors: TAKAHASHI, Makoto, KONISHI, Toshio, MAEDA, Yorinobu, FUKUZAWA, Masataka, NISHIDA, Toshihiro, OHYA, Toshihide, KATAYAMA, Kouji, KAKEHI, Norihiko, SAKAKURA, Hiroo, TAKAGI, Atsushi, MAEDA, Minoru, OHAMA, Hirobumi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-06-1998; Maruzen; Japan Science and Technology Agency
• Subjects: Administration, Oral; Amidohydrolases - metabolism; Animals; Bile - chemistry; bile acid; Bilirubin - chemistry; Biological and medical sciences; Calcium; Calcium Carbonate - chemistry; Chelating Agents - administration & dosage; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chelating Agents - metabolism; cholelithiasis; Cholelithiasis - chemistry; cholelitholytic agent; Digestive system; Drug Stability; Edetic Acid - chemistry; Humans; Injections, Intravenous; Intestinal Mucosa - enzymology; Liver - enzymology; Male; Medical sciences; Pancreas - enzymology; Pancreatin - metabolism; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; ursodeoxycholic acid; Ursodeoxycholic Acid - administration & dosage; Ursodeoxycholic Acid - analogs & derivatives; Ursodeoxycholic Acid - chemical synthesis; Ursodeoxycholic Acid - chemistry; Ursodeoxycholic Acid - metabolism; Biliary stone; Excretion; Intravenous administration; Rat; Rodentia; Oral administration; Dissolution; In vitro; Ursodeoxycholic acid; In vivo; Vertebrata; Mammalia; Calcium Carbonates; Animal; Chelating agent
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.21.551

A novel calcium-chelating agent, N"-ursodeoxycholyldiethylenetriamine-N, N, N'-triacetic acid (UDCA-DTTA), was synthesized to study its ability to dissolve calcified gallstones. The chelating activity of the compound was demonstrated by dissolving calcium carbonate in vitro at a high dissolution rate. In the presence of the agent, sliced human gallstone with a composition of more than 50% calcium bilirubinate was thoroughly dissolved, indicating that calcium bilirubinate was dissolved from the gallstone. The ability to dissolve calcium was comparable to that of EDTA. However, the laminar structure of the sliced gallstone did not disappear in the presence of EDTA, whereas the structure disappeared in the presence of UDCA-DTTA. All these results indicate that UDCA-DTTA is an interesting compound as a parent substance for developing a prodrug for an oral or intravenous agent to dissolve calcium-containing gallstones.