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Biomedical subjects

H Bundgaard

Publications and source records attributed to H Bundgaard.

At least 109 records · Page 6Linked to original sources
PubMed1983

Prodrugs as drug delivery systems XXV: Hydrolysis of oxazolidines--a potential new prodrug type.

The hydrolysis kinetics of several oxazolidines derived from (-)-ephedrine and various aldehydes and ketones were studied to assess their suitability as prodrug forms for beta-amino alcohols and/or carbonyl-containing compounds. The oxazolidines were found to undergo a facile and complete hydrolysis in the pH range of 1-11 at 37 degrees. The hydrolysis rates were subject to general acid-base catalysis by buffer substances and depended strongly on pH. Most oxazolidines showed sigmoidal pH-rate profiles with maximum rates at pH greater than 7-7.5. At pH 7.40 and 37 degrees the following half-lives of hydrolysis for the various ephedrine oxazolidines were found: 5 sec (formaldehyde), 18 sec (propionaldehyde), 5 min (benzaldehyde), 5 sec (salicylaldehyde), 30 min (pivalaldehyde), 4 min (acetone), and 6 min (cyclohexanone). The reaction rates in neutral and basic solutions were shown to decrease with increasing steric effects of the substituents derived from the carbonyl component and to decrease with increasing basicity of the oxazolidines. The oxazolidines are weaker bases (pKa 5.2-6.9) than the parent beta-amino alcohol and more lipophilic at physiological pH. It is suggested that oxazolidines can be considered as potentially useful prodrug candidates for drugs containing a beta-amino alcohol moiety or carbonyl groups.

Buffers↗
PubMed1983

A new spectrophotometric method for the selective determination of ampicillin, amoxycillin and cyclacillin in the presence of polymers and other degradation products.

A rapid and convenient spectrophotometric method is described for the quantitative determination of ampicillin and other amino-penicillins. The method involves conversion of the penicillins to the corresponding piperazine-2,5-dione derivatives by heating in an alkaline sorbitol-zinc ion solution for 10 min at 60 degrees C and subsequent treatment of these derivatives with 1 M sodium hydroxide to give a highly absorbing product with lambda(max) at 322 nm. Since an intact beta-lactam moiety and a free amino group in the side-chain of the penicillin molecules are required for the piperazinedione formation, the method is highly selective. The method was found to be free of interference from polymerization and other degradation products and its application to assess the stability of the amino-penicillins was demonstrated.

Journal Article↗
PubMed1982

Reaction of ampicillin with serum albumin to produce penicilloyl-protein conjugates and a piperazinedione.

Formation of penicilloyl-protein conjugates in the body by reaction of penicillins with nucleophilic groups of proteins is considered to be involved in penicillin allergy. In this study the kinetics and mechanism of reaction of ampicillin with human and bovine serum albumin in aqueous solution at 37 degrees C and pH 6.6-10.4 have been investigated and compared with the reaction of benzylpenicillin previously reported. In addition to forming penicilloyl-protein conjugates, ampicillin was found to react with the proteins to yield a free piperazine-2,5-dione derivative. This product is suggested to arise from intramolecular aminolysis of an N-(penicilloyl)imidazole intermediate at pH 6-8 and of a penicilloyl ester intermediate at higher pH values. The piperazinedione formation was found to compete effectively with formation of penicilloyl-protein conjugates at physiological pH and, along with studies of ampicillin with protein model compounds, the reaction allowed suggestions to be made abut the penicillin-reacting sites in the proteins.

Amines↗
PubMed1980

Prodrugs as drug delivery systems IV: N-Mannich bases as potential novel prodrugs for amides, ureides, amines, and other NH-acidic compounds.

The hydrolysis kinetics of a series of N-Mannich bases of carboxamides, thioamides, and other NH-acidic compounds were studied to assess their suitability as prodrugs for various drugs. The pH-rate profiles for the compounds were determined at 37 degrees and were accounted for by assuming the spontaneous decomposition of both free and protonated Mannich bases. The reaction rate for the free base increased sharply with increasing steric effects of the amine component of the N-Mannich bases and also with increasing acidity of the amide component. N-Mannich bases may be potentially useful prodrugs for NH-acidic compounds such as various amides, and ureides and for amines.

Amides↗
PubMed1977

Polymerization of penicillins. IV. Separation, isolation and characterization of ampicillin polymers formed in aqueous solution.

Polymeric substances formed from ampicillin sodium in aqueous solution have been separated according to charge by anion-exchange chromatography on a column of DEAE-Sephadex A-25 using a linear sodium chloride gradient at a constant pH of 7.4. The separated materials, ranging in size from the monomer to the octamer, have been characterized by various functional-group analyses. A homogeneous well-defined ampicillin dimer, tetramer and hexamer have been isolated from the effluent in high yields. The separation and isolation of the ampicillin polymers permit a conclusive establishment of their structures, which in turn has confirmed previous suggestions that the polymers are formed through a chain process involving aminolysis of ampicillin at the beta-lactam carbonyl moiety by the amino group of the side-chain of a second ampicillin molecule.

Ampicillin↗