Properties of an oral preparation containing a chitosan salt.

The 2-(4-chlorophenoxy)-2-methylpropionic acid (CMP) salt of chitosan (CS), CS-CMP, and that of a CS derivative (CP), were prepared and their ability to adsorb bile acids investigated. CS-CMP and CP-CMP rapidly adsorbed taurocholate (TCA) and glycocholate (GCA) when these bile acids were present together in the medium, with simultaneous release of CMP. A secondary bile acid, taurodeoxycholate, was preferentially adsorbed over TCA and GCA. Alginate gel beads containing CS-CMP did not differ from CS-CMP alone in their manner of bile acids take up. Furthermore, oral administration of CS-CMP to rats resulted in decreased serum cholesterol and triacylglycerol levels for two weeks. Therefore, CS-CMP, as well as a vehicle containing CS-CMP, might be a useful agent with which to treat hyperlipidemia.

The drug release profile from calcium-induced alginate gel beads coated with an alginate hydrolysate.

Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate (Alg), e.g. the guluronic acid block (GB) was prepared and the model drug, hydrocortisone release profiles were investigated under simulated gastrointestinal conditions. Their molecular weights were one sixth or one tenth that of Alg and the diffraction patterns of the hydrolysates resembled that of Alg. The drug release rate from Alg-Ca coated with GB apparently lowered than that of Alg-Ca (coating-free) in the gastric juice (pH1.2). And the coating did not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8) and the gel erosion accelerated the drug release. On the other hand, for the coated Alg-Ca containing chitosan, the drug release showed zero-order kinetics without rapid erosion of Alg-Ca. The drug release rate from Alg-Ca was able to be controlled by the coating and modifying the composition of the gel matrix.

Adsorption of bile acid by chitosan salts prepared with cinnamic acid and analogue compounds.

A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN) was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution, it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with cinnamic acid, the amount of CN released was 0.286 +/- 0.001 mmol/g CS-CN; the amount of taurocholate adsorbed was 0.284 +/- 0.003 mmol/g CS-CN. These two functions were recognized on alginate or pectin gel beads containing CS-CN. The amount of released CN was altered extensively by the species of CN used for gel-bead preparation. Results suggest that CS-CN is a candidate for complementary medicine to prevent lifestyle-related diseases.

Adsorption of bile acid by chitosan-orotic acid salt and its application as an oral preparation.

The orotic acid (OT) salt of chitosan (CS), CS-OT, and that of a CS derivative, CP, were prepared, and the adsorption of primary or secondary bile acid was investigated. Calcium-induced alginate gel beads (Alg-Ca) containing CS-OT were also prepared and autoclaved, and the possibility of these beads to act as a vehicle for oral administration to prevent hyperlipidemia was investigated. When taurocholate (TCA) and glycocholate (GCA) were present together in the medium, CS-OT adsorbed identical amounts of both bile acids. This trend was seen in all CPs, although the capacity to adsorb bile acid was affected by the number and/or structure of the amino groups in the CP. On the other hand, taurodeoxycholate, a secondary bile acid was preferentially adsorbed over TCA and GCA. Alg-Ca containing CS-OT took up bile acids in a similar manner as CS-OT irrespective of the water content of the gel matrix. As all elements can be taken as a food, Alg-Ca containing CS-OT could serve as a useful dietary agent for the prevention of hyperlipidemia, which is a lifestyle-related disease.

Properties of calcium-induced gel beads prepared with alginate and hydrolysates.

Calcium-induced alginate gel beads (Alg-Ca) containing alginate hydrolysate, such as the guluronic acid block (GB), was prepared and the drug release profiles were investigated under simulated gastrointestinal conditions. The addition of GB to Alg-Ca altered its rheological properties. A model drug (hydrocortisone) was incorporated at 78% of its theoretical yield within the dried Alg-Ca containing 5% GB and it was gradually released from the beads in JP XIV 1st medium for disintegration test (pH 1.2), while it was rapidly released with disintegration of the gel matrix in JP XIV 2nd medium (pH 6.8). In contrast, for Alg-Ca containing GB and chitosan, disintegration was not observed in these media and the drug release rate was markedly different. These results demonstrate that the release profiles of drugs incorporated into Alg-Ca can be controlled by adding these polysaccharides.

Drug release properties of a gel bead prepared with pectin and hydrolysate.

A calcium-induced pectin gel bead (PB) containing pectin hydrolysate was prepared, and the drug release profiles and degradation properties of the PB were investigated in aqueous media. The stiff PB swelled in physiological saline and its drug release rate decreased with exposure to increasing concentrations of CaCl2 during preparation. And erosion of the PB was not observed in physiological saline. However, the PB did disintegrate in phosphate buffer (pH 6.8) and the rate of disintegration depended on the calcium chloride concentration used to prepare the PB. In addition, the drug release rate of the PB in buffer solution decreased as the rate of gel erosion declined. Consequently, it appears that the PB gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.