Accelerated Ulcer Healing via Activation of Endogenous Tissue Repairing Factors by Sulfated Cyclic Oligosaccharides

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Tissue repairing factors including basic fibroblast growth factor (bFGF) exist as naturally occurring peptides in gastric and duodenal mucosa, and they nay act to prevent ulceration unless these peptides are excessively degraded by gastric juices. The objective of this study, thesefore, is to investigate the potential use of water-insoluble aluminium salts of sulfated cyclic oligosaccharides for modulating the tissue repairing factors. The results obtained were as follows.1. Sulfated cyclic oligosaccharides had a high affinity for bFGF and protect it from proteolytic degradation. These sulfated cyclic oligosaccharides may electrosatically bind close to the putative heparin binding domain, a cluster of several basic amino acid residues, on the surface of the bFGF molecule.2. The mitogenic activity of bFGF released from its adsorbate with aluminium salts of sulfated cyclic oligosaccharides was almost comparable with thay of the intact protein, as indicated by the proliferation of kidney cells of baby hamsters (BHK-21) .3. The oral administration of alminium salts of sulfated cyclic oligosaccharides tended to enhance the healing rate of aceticacid-induced gastric ulcers and cysteamine-inducedduodenal ulcers. In particular, the aluminium salts of sulfated cyclic oligosaccharides loaded with bFGF had the most prominent healing effects on the ulcers.These results suggest that the aluminium salts of sulfated cyclic oligosaccharides have a potent therapeutice efficacy for wound healing via stabilization of endogenous tissue repairing factors and can be applicable to the treatment of intestinal mucosal erosions.