HYDROXYALKYL CYCLODEXTRIN-ANTIFUNGAL POLYENE ANTIBIOTICS COMPLEXES

摘要

The present invention involves a composition of matter comprising amphotericin B and hydroxyalkyl-gamma-cyclodextrin. The hydroxyalkyl-gamma-cyclodextrin is preferably hydroxypropyl-gamma-cyclodextrin, most preferably 2-hydroxypropyl-gamma-cyclodextrin. The cyclodextrin utilized in the practice of the present invention comprises rings of eight glucose units bound in 1-4 glucosidic linkages, each glucose unit having a hydroxyalkyl radical in ether linkage. The hydroxyalkyl radical is bound in ether linkage to carbon-5 of the glucose unit. The composition of matter of the present invention preferably comprises a cyclodextrin ring of eight glucose units bound in 1-4 glucosidic linkages, substantially each glucose unit having a 2-hydroxypropyl radical in ether linkage. The present invention also involves a method for the treatment of an animal with fungal infection. This method comprises administering to the animal a fungicidally effective amount of a composition of matter as described above comprising amphotericin B and hydroxyalkyl-gamma-cyclodextrin. The administration is preferably parenteral, particularly for disseminated fungal infection, but could be internal or topical, depending upon the particular site of fungal infection and desires of the treating physician. The disseminated fungal infection most preferably treated is a yeast infection such as a Candida albicans, Candida tropicalis, Candida parapsiloses or Torulopsis glabrata infection. The fungicidally effective amount useful for treatment of disseminated fungal infection contains between about 0.4 mg amphotericin B per kg body weight and about 4.0 mg amphotericin B per kg body weight.