Takeda Chemical Industries, Inc.

Akihiro Nagai

Nobuyuki Takechi

Seiji Ohtani

Naoru Hamaguchi

Hisayoshi Shimizu

Yoshiharu Matukura

Etsunosuke Noda

Yasushi Mikura

Yoshihiko Tsugawa

Yoshihiro Ohmachi

Disclosed is a method of producing microspheres which comprises subjecting a w/o/w emulsion or o/w emulsion to an in-water drying method under the following conditions:

Sustained release microspheres and preparation thereof

Production of microspheres

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.

Method of producing highly water-soluble cyclodextrin complex

This invention comprises a pharmaceutical composition comprising a benzimidazole compound having antiulcer activity and a water-soluble carboxylic acid amide. According to this invention, a water-insoluble benzimidazole compound having antiulcer activity can be solubilized and a stable pharmaceutical composition can be provided. The solid pharmaceutical composition of this invention can be extemporaneously dissolved in sterile distilled water or an infusion (e.g. physiological saline, glucose infusion, etc.) and put to use as an injection with great convenience.

Pharmaceutical composition

An injectable solution of a compound useful as an anti-ulcer agent of the formula; ##STR1## wherein R.sup.1 represents hydrogen, methoxy or trifluoromethyl group; R.sup.2 and R.sup.3, being the same as or different from each other, represent hydrogen or methyl group; and R.sup.4 represents a fluorinated C.sub.2 to C.sub.5 lower alkyl group, is provided by dissolving the compound in at least one of ethanol, propylene glycol and polyethylene glycol; or by dissolving the freeze-dried material of an alkaline aqueous solution of the compound in a mixture of an acidic substance and at least one of the above solvents.

Injectable solution containing a pyridyl methylsulfinylbenzimidazole

The present invention relates to a stabilized aqueous suspension of oxendolone, which contains 0.05 to 1.0 w/v percent of a nonionic surfactant and 0.01 to 0.25 w/v percent of a p-hydroxybenzoic acid ester. The suspension satisfy the requirements of a pharmaceutical preparation and shows a prolonged activities of oxendolone without accompanying pain when it is injected.

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Osaka, Japan

Akihiro Nagai