Aqueous pharmaceutical compositions

#The present invention relates to an antibacterial aqueous pharmaceutical composition and an aqueous pharmaceutical composition which have a sufficiently low gelation temperature even when new quinolone antibacterial agents such as ofloxacin as the active ingredient and can be retained at the administration site for a long time by virtue of rapid gelation rate which leads to rapid viscosity increase after administration in spite of their being liquid at administration, and thereby attain high availability of pharmaceutical agent.

#Since a majority of a pharmaceutical agent is flown from eyes to nose when the pharmaceutical agent is administered to eyes, study to stay a pharmaceutical agent on the surfaces of eyes as long time as possible by increasing the viscosity of a preparation has been progressed. In order to increase the viscosity of a preparation, a polymer compound is generally added. However, when the viscosity of a preparation is increased, there arises dispersion in an administration amount, and such defect is caused that administration of a constant amount becomes difficult.

#The viscosity of an aqueous solution of a polymer compound is generally lowered when a temperature is arisen. However, an aqueous solution of methylcellulose (MC), hydroxypropylmethylcellulose, poly(vinyl alcohol) or the like has the characteristic that it is gelled and the viscosity is increased at a certain temperature or a higher temperature.

#[Gelation Behavior of OFLX-containing Thermally Gelling Preparation]

#Methylcellulose (manufactured by Shin-Etsu Chemical, Metolose (registered trademark) SM-4, the viscosity of a 2 w/v % aqueous solution at 20° C. is 3.2 to 4.8 mPa.s) and polyethylene glycol (Macrogol 4000, manufactured by NOF Corporation) were mixed at a prescribed amount, sterile purified water heated to 85° C. was added thereto, and the mixture was stirred to disperse the ingredients. After confirmed that the ingredients were uniformly dispersed, the dispersion was ice-cooled while stirring. After confirmed that the whole became clear, prescribed amount of sodium citrate was gradually added, and was dissolved with stirring. Furthermore, a prescribed amount of ofloxacin (OFLX, final incorporation amount 0.3 w/v %) was added, and dispersed therein by stirring. To this was gradually added 1N HCl while stirring until the whole became clear. Furthermore, 1N HCl was added, pH was adjusted to 6.5, and sterile purified water was added to a prescribed volume to prepare the 0.3 w/v % OFLX thermally gelling preparation of the present invention.

#Separately, the 0.3 w/v % OFLX thermally gelling preparation for comparison was prepared according to the same manner as that for the aforementioned thermally gelling preparation of the present invention except that methylcellulose was changed from SM-4 to SM-15 (manufactured by Shin-Etsu Chemical, Metolose (registered trademark), the viscosity of a 2 w/v % aqueous solution at 20° C. is 13 to 18 mPa.s).