title: DMSO preparation as a direct solubilizer of calcium bilirubinate stones.
abstract: Despite considerable progress in operative techniques, biliary surgeons continue to encounter difficulties when treating patients with intrahepatic gallstones. We have experienced a significant number of patients in whom complete stone removal was impossible during an operation due to the anatomical complexity of intrahepatic bile ducts, and the variety in the size and hardness of the stones. Under such circumstances, the application of a direct solubilizer capable of dissolving intrahepatic calcium bilirubinate stones, might be a possible alternative. Up to now, however, only calcium chelating agents have been used for removing calcium from calcium bilirubinate stones, and they are not always effective. As a promising solution to this problem, we have now developed a direct solubilize for bilirubin complexes--a dimethyl sulfoxide (DMSO) preparation. DMSO is a well-known bipolar nonprotonic solvent. We prepared solutions of DMSO and performed toxicological studies by administering this preparation to rats and dogs. Biochemical indices of liver and renal function remained unchanged after 7-28 days of DMSO administration. Nor were there any histological changes in the DMSO-treated animals on systemic survey of various organs. On comparing the in vitro capability for solubilizing calcium bilirubinate stones, the DMSO preparation was consistently superior to a calcium chelating agent alone. The combination of a chelating agent with DMSO had the highest solubilizing capacity.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Igimi
authors.forename: S
authors.initials: S
authors.lastname: Asakawa
authors.forename: R
authors.initials: R
authors.lastname: Tamura
authors.forename: F
authors.initials: F
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Shimura
mesh_terms: D000818:Animals; D001653:Bile Ducts, Intrahepatic; D001663:Bilirubin; D002769:Cholelithiasis / Q000737:chemistry / Q000628:therapy*; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use* / Q000633:toxicity; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D001663:Bilirubin; D004121:Dimethyl Sulfoxide