Abstract: Novel non-ionic contrast media of a hitherto unknown combination of low osmolality and low viscosity are efficiently prepared from generally available ionic contrast media or non-iodinated precursors. Particularly, polyhydroxyhalo-hydrocarbons are employed with a triiodo-substituted acylamido benzoic acids in aqueous weakly basic media to selectively substitute the amido nitrogen, followed by activation of the carboxyl group for amide formation.

Abstract: Methods and compositions are provided for producing sterile drug formulations, where drugs are thermolabile and pH sensitive. The method provides formulating the drug with a physiologically acceptable inorganic or organic acidic buffer for buffering at a pH in excess of 6, reducing the pH below about 5 by adding carbon dioxide, and heat sterilizing the formulation in a gas permeable sealed container. The resulting formulation is substantially free of degraded drug and at the desired physiologically acceptable pH. Also, formulations are provided which do not cause clotting during administration.

Abstract: Methods and compositions are provided for preparing polyhydroxylated polyiodo non-ionic contrast media. Particularly, substituted polyiodobenzamides are prepared, wherein the benzamide nitrogen is polyhydroxylated by allylic substitution on the nitrogen and oxidation of the olefinic group to provide for polyhydroxyl substitution. Amino substituents on the benzamide may be polyhydroxylated by allyl substitution or acryl substitution. All of the olefins may be oxidized simultaneously to glycols to provide for water soluble relatively non-toxic contrast media in efficient economical processes. Alternatively, the same compounds can be synthesized by alkylating N-acylbenzamide with polyacetoxyalkyl or dioxolanylalkyl halides, followed by removal of the protective groups.

Abstract: Novel intermediates for non-ionic polyiodo amino-substituted benzenepolyamides having polyol substituents on the amide nitrogens are provided which are 5-amino-6-hydroxy-1,3-dioxepanes. The compounds provide an economic and efficient route to novel contrast media having excellent chemical and physiological properties.Also provided are methods for preparing the subject compounds.

Abstract: Novel methods are provided for synthesizing 2-amino-2-tetritol, by positive halogen addition to protected 1,4-dioxybutene-2 in the presence of a nitrile, resulting in addition of a halo functionality and the nitrile functionality across the double bond. Upon hydrolysis, the desired erythro-product can be obtained in stereochemically good yield.

Abstract: Novel intermediates for non-ionic polyiodo amino-substituted benzenepolyamides having polyol substituents on the amide nitrogens are provided which are 5-amino-6-hydroxy-1,3-dioxepanes. The compounds provide an economic and efficient route to novel contrast media having excellent chemical and physiological properties.Also provided are methods for preparing the subject compounds.

Abstract: Non-ionic polyiodo saccharidic ether substituted anilines are provided as contrast media, the ether being non-glycosidyl. The compounds have excellent physical properties in having acceptable water solubility or capable of stable suspension, relatively low osmotic pressure, good thermal stability, so as to be heat sterilizable, and a high iodine proportion. The compounds can be prepared from polynitroaromatics by substitution and reduction.