A STUDY OF THE ANTIPEPSIN ACTIVITY OF MAJOR ANTACID COMPOUNDS
Abstract
Pepsin activity was maximum at pH 2.2-2.6 and became minimal at pH4. Sodium, calcium, magnesium, aluminum, and aluminum chlorohydrate cations had no significant effect on pepsin activity. Rapidly reacting antacid compounds--sodium bicarbonate, calcium carbonate, and magnesium hydroxide--could exist in gastric fluids as soluble ions and would not have a specific antipepsin effect. Aluminum hydroxide reacts slower and would be partially present in the gastrointestinal tract as a colloid. Gibbsite and boehmite, nonacid-reactive oxyaluminas, absorb pepsin, and the extent was pH dependent, maximum at pH3. Boehmite has a higher binding capacity due to its larger surface area. Partial desorption by phosphate indicated strong binding forces, multidentate ligand exchange supplemented by hydrogen bonding and van der Waals forces. Pepsin adsorbed was quantified by carbon-nitrogen microanalysis and spectroscopy. Pepsin absorbed on gibbsite and boehmite had significantly lower activity than soluble pepsin. Infrared and desorbed pepsin activity studies indicated that pepsin was not denatured on the surface. Infrared studies suggested possible conformational changes in adsorbed pepsin resulting in reduced acitivity. Activity of pepsin adsorbed on gibbsite was equivalent against either hemoglobin or N-acetyl-L-phenylalanyl-L-3,5-di-iodotyrosine. Pepsin adsorbed on boehmite produced similar results to pepsin adsorbed on gibbsite for the dipeptide but had a significantly lower activity using hemoglobin. This greater reduction in activity was due to differences in adsorbent morphology. SEM and TEM showed gibbsite to have a smooth surface and boehmite to be a porous material. Steric occlusion of the active site was believed to lower the activity of pepsin adsorbed on gibbsite. Besides steric occlusion, steric exclusion and diffusional resistance of hemoglobin due to the porous network caused the lower activity of pepsin adsorbed on boehmite. Physiological phosphate concentrations did not substantially affect pepsin adsorption indicating applicability to biological systems. Pepsin decreased the acid neutralization rate of aluminum hydroxide gels by adsorbing and retarding proton-gel interaction. An ideal antacid product should contain (1) an acid reactive component to neutralize gastric acid and raise gastric pH and (2) a nonacid reactive component to adsorb pepsin providing a specific antipepsin effect and also adsorb other irritants.
Degree
Ph.D.
Subject Area
Pharmaceuticals
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.