The favorable bile acid binding characteristics of sevelamer provide a compelling explanation for its ability to lower LDL cholesterol in hemodialysis patients and in healthy volunteers.

In vitro binding studies demonstrate that RenaGel has an extremely high phosphate binding capacity. At an estimated physiological concentration of 5 mM phosphate, RenaGel binds 2.6 mmole phosphate/g of phosphate binder. The in vivo binding study shows that RenaGel mixed into the diet decreased urinary phosphorus excretion in a dose dependent manner. RenaGel particles with a 23 microns mean diameter are more efficacious than the larger ones. In conclusion, the above studies indicate that RenaGel is a potent phosphate binder. RenaGel contains no calcium or aluminum and offers an alternative to existing phosphate binder treatments.

Iron overload is a severe clinical condition and can be largely prevented by the use of iron-specific chelating agents. A successful iron chelator needs to be orally active, nontoxic, and selective. In this study, hydrogels containing pendant hydroxamic acid groups have been synthesized as potential nonabsorbed chelators for iron in the gastrointestinal tract. The synthetic method employed to introduce hydroxamic acid groups to polymer chains involved reaction of polymer gels based on N-acryloxysuccinimide, acryloyl chloride, and (2-hydroxyethyl)acrylate monomers with hydroxylamine. These hydroxamic acid-functionalized polymer gels swell favorably in water and effectively sequester iron. In vitro iron-binding properties of these hydrogels were evaluated from their binding isotherms by use of iron(II) alone and in the presence of other competing metal ions. These polymers bind iron over a broad pH range. The iron-binding properties of the polymers were found to depend on the concentration of hydroxamate groups on polymer chains. The in vivo iron-binding efficacy of the polymers was evaluated in rat as the animal model. The polymers prevented an increase in serum hemoglobin and hematocrit levels in the animals, thus suggesting the prevention of systemic absorption of dietary iron from the gastrointestinal tract. The animals also maintained normal body weight during the treatment period, indicating the absence of any apparent toxicity associated with these polymers.

Solutions obtained by mixing 1 equiv of organo(ligand)copper(I) reagent (organo = n-butyl, sec-butyl, tertbutyl, phenyl, and 1-pentynyl) with 1 equiv of an organolithium reagent having a different organic group have been allowed to react with 1-bromopentane, methyl vinyl ketone, and nitrobenzene. The relative yields of products observed in these reactions of "mixed" lithium diorganocuprates, "R1R2CULÍ," are summarized and used to infer the relative reactivities of the two organic groups in these complexes. Organic moieties that form stable, unreactive, copper® compounds (1-pentynyl, tert-butoxyl, aryl) show the smallest reactivity in these cuprates and are the most generally useful first components for mixed ate complexes in which it is intended that the second component react preferentially with substrate. However, use of these groups has one drawback in reactions involving certain substrates of low reactivity: the reactivity of the second organic group in the mixed complex is significantly decreased by inclusion in the complex, relative to that which would be expected from the corresponding symmetrical cuprate. If mixed cuprates made from stable organocopper compounds show insufficient reactivity, mixed complexes containing a highly basic organic group, particularly tert-butyl, may have advantages. A survey of the relative reactivity of several alkyl bromides toward lithium di-n-butylcuprate establishes a structure-rate profile for nucleophilic coupling characteristic of an Sn2 reaction. 93 sec-C4H9 49585-84-4 23, 45I.

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