Oral administration of a new soluble branched β-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers

摘要

The soluble branched yeast β-1,3-D-glucan (SBG) belongs to a group of carbohydrate polymers known to exert potent immunomodulatory effects when administered to animals and humans. A new oral solution of SBG has been developed for local application to the oropharyngeal and oesophageal mucosa in order to strengthen the defence mechanisms against microbial and toxic influences. In the present study oral administration of SBG has been investigated primarily for assessment of safety and tolerability in an early phase human pharmacological study (phase I). Eighteen healthy volunteers were included among non-smoking individuals. The study was an open 1: 1: 1 dose-escalation safety study consisting of a screening visit, an administration period of 4 days and a follow-up period. Groups of six individuals received SBG 100 mg/day, 200 mg/day or 400 mg/day, respectively, for 4 consecutive days. The dose increase was allowed after a careful review of the safety data of the lower dose group. No drug-related adverse event, including abnormalities in vital signs, was observed. By inspection of the oral cavity only minor mucosal lesions not related to the study medication were seen in seven subjects. Repeated measurements of β-glucan in serum revealed no systemic absorption of the agent following the oral doses of SBG. In saliva, the immunoglobulin A concentration increased significantly for the highest SBG dose employed. SBG was thus safe and well tolerated by healthy volunteers, when given orally once daily for 4 consecutive days at doses up to 400 mg.