DRUG INTERACTION WITH INORGANIC SURFACES AND POLYMERIC COLLOIDS (BISBIGUANIDES, POLYMETHYL VINYL ETHER)

WU-HUANG YANG, Purdue University

Abstract

Part I. Binding Studies of Bisbiguanides to Hydroxyapatite and Human Teeth and Characterization of Bisbiguanide Staining Reaction in the Mouth. Bisbiguanides, a series of potent antibacterial agents, which were discovered in 1954, have been extensively tested for applications in oral hygiene. One of the side effects of the repeated use of bisbiguanide-containing mouthwashes and other oral products is the staining of the teeth and the tongue. The staining of the teeth can be reversed by mechanical procedures such as brushing. The staining however remains as an annoying esthetic problem. The chemical nature and the machanism of the staining of human teeth by chlorhexidine and alexidine, two bisbiguanide compounds used in oral hygiene were studied, with the objective of suggesting methods of resolving or preventing the stain formation. The colored compounds which were obtained after incubating alexidine or chlorhexidine with various carbonyl compounds were isolated and identified as Schiff base type compounds. The hypothesis was proposed that these Schiff base type compounds are responsible for the staining of human teeth since carbonyl compounds are the intermediates normally found in both mammalian and microbial metabolism. Langmuir adsorption theory provided an explanation for the sorption phenomenon of alexidine and chlorhexidine on hydroxyapatite and extracted human teeth. It was found that hydroxyapatite was a good model for extracted human teeth in the sorption study. The electrostatic attraction force between the negatively charged hydroxyapatite surface and the positively charged alexidine species was found to be the major driving force for the adsorption of alexidine. A theoretical model for the teeth stain formation with bisbiguanides, which was consistent with the experimental results was developed, as follows: (a) The positively charged alexidine species was adsorbed to the negatively charged tooth surface by the driving force of electrostatic attraction, and (b) the biguanido group at the other end of the bisbiguanide species then reacted with a carbonyl compound normal to the flora of the mouth to form a colored Schiff base type compound. As suggested from the theoretical model, poly(methylvinyl ether/maleic anhydride) was investigated as a potential stain-inhibiting agent, with the idea of providing the bisbiguanide with a large counterion so that the approach of the carbonyl compounds to the bisbiguanide was retarded, and the formation of the stain was thereby minimized or eliminated. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI

Degree

Ph.D.

Subject Area

Pharmaceuticals

COinS