Takeda Chemical Industries, Inc.

Yoshihiro Ohmachi

Akihiro Nagai

Yoshihiko Tsugawa

The present invention provides 1) a method of producing a complex of a fumagillol derivative of the formula: ##STR1## wherein R.sup.1 is hydrogen; R.sup.2 is halogen, N(O)mR.sup.5 R.sup.6, N+R.sup.5 R.sup.6 R.sup.7.X-- or S(O)nR.sup.5, wherein R.sup.5, R.sup.6 and R.sup.7 are independently an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X-- is a counter anion; m is 0 or 1; n is an integer of 0 to 2; and R.sup.5 and R.sup.6 together with the adjacent nitrogen or sulfur atom may form an optionally substituted nitrogen- or sulfur-containing heterocyclic group which may form a condensed ring; or R.sup.1 and R.sup.2 are combined to represent a chemical bond; R.sup.3 is 2-methyl-1-propenyl group or isobutyl group; A is oxygen or NR.sup.8, wherein R.sup.8 is hydrogen or an optionally substituted lower alkyl or aryl group; and R.sup.4 is hydrogen, an optionally substituted hydrocarbon group or an optionally substituted acyl group; or a physiologically acceptable salt thereof, with a highly water-soluble cyclodextrin derivative, which comprises mixing the fumagillol derivative or a physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative into an aqueous solution, the concentration of the highly water-soluble cyclodextrin derivative being at about 100 mg/ml or more, and 2) the complex of the fumaggillol derivative (I) or physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative obtained by the production method 1). The complex of the fumagillol derivative (I) or physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative is highly soluble in water, highly stable in storage and can be used as a preparation for injection.

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Tsukuba, Japan

Yoshihiro Ohmachi