| 摘要 |
The disclosure relates to a composition comprising stannsoporfin, wherein said stannsoporfin is at least 97.0% pure and where any individual impurity present is present in an amount of less than 0.1 %, and wherein the composition contains less than 20 ppm of palladium, and wherein the composition has a pH of 7.0 to 8.0, and wherein the composition may further comprise a buffer selected from a phosphate, citrate, gluconate, lactate, tartrate, glycinate, glycylglycinate, bicarbonate, carbonate, maleate, acetate, histidine, imidazole and combinations thereof. Said composition is suitable for treating a condition selected from hyperbilirubinemia or elevated serum levels of bilirubin in a subject. Also disclosed is a method for producing a tin (IV) mesoporphyrin compound or salt thereof comprising: (a) preparing a solution or suspension of mesoporphyrin IX dihydrochloride or a salt thereof by: (1) exposing a metallic hydrogenation catalyst to a hydrogen atmosphere to form a pre-hydrogenated catalyst, wherein the metallic hydrogenation catalyst is palladium on carbon; and (2) contacting hemin with the pre-hydrogenated catalyst and maintaining the hemin and catalyst under one or more combinations of temperature, hydrogen pressure, and time to remove iron from the hemin and to reduce the vinyl groups of the hemin to ethyl groups, thus forming mesoporphyrin IX, (3) isolating the mesoporohyrin IX as mesoproxphyrin IX formate; (4) purifying the isolated mesoporphyrin IX formate; (5) converting the purified mesoporphyrin IX formate into mesoporphyrin IX dihydrochloride: (6) treating the mesopoxphyrin IX dihydrochloridewith diatomaceous earth and activated carbon, then adding 0.1 to 6N HCI to the mesoporphyrin IX dichloride; (b) preparing a solution or suspension of tin (II) oxide, wherein steps (a) and (b) can occur in any order or simultaneously; (c) contacting the solution or suspension of tin (II) oxide with the solution or suspension of mesoporphyrin IX dihydrochloride or salt thereof by dropwise addition of the solution or suspension of mesoporphyrin IX dihydrochloride or salt thereof to form the tin (IV) mesoporphyrin compound or salt thereof; and (d) purifying the tin (IV) mesoporphyrin IX dichloride via hot acid trituration, followed by, treatment at high pH at or above pH 9 followed by re-acidification, and subsequent hot acid trituration. |
