新抗真菌性抗生物質"Copiamycin"の試験管内,生体内作用の研究

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A new antifungal antibiotic "Copiamycin" was discovered by Arai et al. in 1965 from the fungal body of Streptomyces hygroscopicus var. crystallogenes grown in Soybean meal medium. Copiamycin is a non-polyenic antibiotic obtained as colorless platelets and active against a wide variety of pathogenic and non-pathogenic yeast and fungi. Because the antibiotic is almost insoluble in water and in order to attain practical application of this antibiotic, several water soluble derivatives were prepared and supplied by the research staff of the Kyowa Fermentation Go. Ltd. These are Acetyl-Cop, Propionyl-Cop, Cop-HNO_3, Cop-HCl, Cop-1/2H_2SO_4, Cop-1/3 H_3PO_4, 2H-Cop-HCl, 4H-Cop-HCl, Ac-2 H-Cop, and Ac-4H-Cop. Biological activities of these water soluble derivatives as well as two hydrogenated products, 2H-Cop and 4H-Cop were compared in vitro and in vivo. Antimicrobial activities of Cop-HNO_3, Gop-1/3H_3PO_4, 2H-Cop, Prop-Cop on pathogenic fungi were almost equal to Copiamycin base, whereas other derivatives of Copiamycin exhibited less activities than Copiamycin base. Trichomanas vaginalis was also killed or inhibited by relatively low concentrations of Propionyl and Acetyl-Copiamycin. When the acute toxicity of these derivatives were tested in mice, it was found that water soluble Copiamycin derivatives showed higher toxicity than water insoluble preparations, and intravenous administration was most toxic and oral administration was almost non-toxic. Addition of serum to the medium decreased antimicrobial activity of Copiamycin. The activity was the highest at slightly alkaline pH. When mice infected with Candida albicans were treated with Copiamycin, the prolongation of life span was observed. However, the effect of Copiamycin was much less than that of Amphotericin B. Excellent therapeutic effect was obtained in the treatment of guinea pig Trichophytosis with the ointment or tincture of Ac-Cop and 2H-Gop.

No irritation was noticed when 100mg of 1% Ac-Cop ointment was applied to the mucous membrane of rabbit's eyes for 7 successive days. Patch test on human skin gave negative results. Clinical trials of Copiamycin or Ac-Cop vaginal tablets and ointment to vaginal candidiasis and to dermatomycosis, respectively, also proved to be successful.