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KMID : 0369819920220020097
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Jorunal of Korean Pharmaceutical Sciences
1992 Volume.22 No. 2 p.97 ~ p.104
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Effect of Fatty Acid Salts on Proteolysis of Insulin in the Nasal Tissue Homogenates of Rabbits
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한건/Han K
차철희/정연복/박정숙/Cha CH/Chung YB/Park CS
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Abstract
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The purpose of this study was (i) to determine whether protease inhibition by medium chain fatty acids such as sodium caprate, sodium caprylate and sodium laurate led to suppression of insulin proteolysis over a range of insulin concentrations and (ii) elucidate preventing effect of the enhancers on molecular self-association of insulin in pH 7.4 phosphate buffer isotonic solution. To this end, the rate of insulin proteolysis in nasal tissue supernatants of the albino rabbits was determined in the presence of 0.1∼2 sodium caprylate, sodium caprate and sodium laurate at insulin concentrations ranging from 5to100μM. At fatty acid salts concentration lower than 0.5%, insulin proteolysis was accelerated but the enhancers of high concentration (>1%) reduced the rate of insulin proteolysis. These effects were dependent upon insulin concentration and chain length of fatty acid salts. Circular dichroism spectra of insulin solutions were then determined. Monomer fraction of insulin was increased with increasing sodium caprate. Therefore, half-life decrease of insulin at low concentrations of the enhancers was attributed to deaggregation of insulin by the enhancers, increasing the proportion of monomers available for nasal proteolysis. And the increase of half-life at high concentration of the enhancers was attributed to inhibitory effect on protease rather than the effect of monomer fraction.
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KEYWORD
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nasal absorption, insulin, penetration enhancer, fatty acid salt, molecular, self-association, nasal proteolysis
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