含そう用アロプリノール液に使用する保存剤の検討

Abstract

For the prevention or treatment of stomatitis caused by anticancer agents, allopurinol gargle has been used at Gifu University Hospital. The allopurinol gargle has been prepared by dispersing powdered allopurinol tablets and sodium carboxymethylcellulose into water for injection. As the result of examination of microbial contamination of the allopurinol gargle administered to a patient, Acinetobacter calcoaceticus var. anitratus, Burkholderia pickettii or Candida albicans were isolated. Benzoic acid (BA), sodium dehydroacetate (DA) and ethyl-p-hydroxybenzoate (EP) were used as preservatives for allopurinol gargle. Allopurinol gargles containing 0.05% of BA, 0.1 % of BA, 0.05% of DA, 0.1 % of DA or 0.05% of EP were prepared and antimicrobial activities against strains isolated from allopurinol gargles and those from clinical specimens were assessed based on the criteria for topical preparations in British Pharmacopoeia. Among the alloprinol gargles prepared, only alloprinol gargle containing 0.1% of BA had antimicrobial activity against all strains at storage conditions of 25°C and 37°C. The alloprinol gargle containing 0.1 % of BA did not demonstrate sufficient antimicrobial activity at 4°C. The BA added to allopurinol gargles had no influence on either the stability of allopurinol or on the inhibition of xanthine oxidase by allopurinol. No growth of organisms appeared in the remaining allopurinol gargle containing 0.1 % of BA used by the patient.These findings suggest that the addition of BA at the concentration of 0.1 % is suitable for allopurinol gargle.