the acid is preferably lactic acid , acetic acid or hydrochloric acid , and the alkali is preferably sodium hydroxide or potassium hydroxide . the concentration of quinolinecarboxylic acid derivative in the solution to be refrigerated may be within a range from 0 . 1 to 30 w / v %, preferably from 5 to 15 w / v %. if the concentration is less than 0 . 1 w / v %, the volume of the solution becomes too large and a large vessel or a large injector will be required , which is inconvenient . on the other hand , if the concentration is higher than 30 w / v %, freeze - drying becomes difficult since the solution cannot be frozen easily by refrigeration . the solution may be sterilized by filtration through a membrane filter ( pore size 0 . 22 μm ) and then be filled into vials . the solution in the vials is cooled to below - 40 ° c . as a general procedure , the vials are directly cooled by contacting with a refrigerant so as to obtain a rapid cooling . the cooling condition can be selected according to the ability of refrigerant and / or refrigerator , but no limitation is needed with respect to the cooling condition . whatever condition to refrigerate the solution to below - 40 ° c . is applicable . the freeze - drying can be performed according to conventional procedures and conditions under a vacuum using vacuum pump and mild elevation of temperature . as for the freeze - drying method , the conventional heat shock method or a method characterized by adding a solvent can also be used . after drying is completed , the vials are sealed , for example , with rubber stopper . medically usable adjuvants may be added to the freeze - dried pharmaceutical preparations of the present invention , such as excipients , adjuvants to provide isotonicity , ph adjusters , stabilizers , solubilizers , buffering agents and preservatives . the excipients or adjuvants providing isotonicity may be xylitol , d - sorbitol , d - mannitol , fructose , glucose , sucrose , lactose , gelatin , and the like . the ph adjuster may also be lactic acid , acetic acid , hydrochloric acid , sodium hydroxide or potassium hydroxide . the following examples illustrate the present invention , but are not intended to limit its scope . in the following examples , the quinolinecarboxylic acid derivatives used are 6 , 8 - difluoro - 1 -( 2 - fluoroethyl )- 1 , 4 - dihydro - 7 -( 4 - methyl - 1 - piperazinyl )- 4 - oxo - 3 - quinolinecarboxylic acid ( hereinafter referred to as am - 833 ), 1 - ethyl - 6 - fluoro - 1 , 4 - dihydro - 4 - oxo - 7 -( 1 - piperazinyl )- 3 - quinolinecarboxylic acid ( hereinafter referred to as nflx ), 9 - fluoro - 2 , 3 - dihydro - 3 - methyl - 10 -( 4 - methyl - 1 - piperazinyl )- 7 - oxo - 7h - pyrido [ 1 , 2 , 3de ][ 1 , 4 ]- benzoxazine - 6 - carboxylic acid ( hereinafter referred to as oflx ), 1 - cyclopropyl - 6 - fluoro - 1 , 4 - dihydro - 4 - oxo - 7 -( 1 - piperazinyl )- 3 - quinolinecarboxylic acid ( hereinafter referred to as cpfx ), 1 - ethyl - 6 - fluoro - 1 , 4 - dihydro - 4 - oxo - 7 -( 1 - piperazinyl )- 1 , 8 - naphthyridine - 3 - carboxylic acid ( hereinafter referred to as enx ), 7 -( 3 - amino - 1 - pyrrolidinyl )- 8 - chloro - 1 - cyclopropyl - 6 - fluoro - 1 , 4 - dihydro - 4 - oxo - 3 - quinolinecarboxylic acid ( hereinafter referred to as am - 1091 ), 1 - ethyl - 6 , 8 - difluoro - 1 , 4 - dihydro - 7 -( 3 - methyl - 1 - piperazinyl )- 4 - oxo - 3 - quinolinecarboxylic acid ( hereinafter referred to as ny - 198 ), 7 -( 3 - amino - 1 - pyrrolidinyl )- 1 -( 2 , 4 - difluorophenyl )- 6 - fluoro - 1 , 4 - dihydro - 4 - oxo - 1 , 8 - naphthyridine - 3 - carboxylic acid p - toluene - sulfonic acid hydrate ( hereinafter referred to as t - 3262 ). ten grams of powdered am - 833 were dissolved in 50 ml of 1m lactic acid , the ph was adjusted to 4 . 5 with 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ) and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 42 ° c ., and dried under vacuum . the temperature of the shelf was kept at - 20 ° c . during the initial stage ( up to 22 hours ) of drying . under vacuum , the temperature was elevated to 20 ° c . and kept for 24 hours , and it was further elevated to 40 ° c . and kept for 6 hours to give a freeze - dried pharmaceutical preparation containing am - 833 . fifteen grams of powdered am - 833 were dissolved in 75 ml of 1m lactic acid , the ph was adjusted to 4 . 0 with 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 1 . 33 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing am - 833 . ten grams of powdered am - 833 and 10 grams of glucose were dissolved in 50 ml of 1m lactic acid , the ph was adjusted to 4 . 5 with 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . the temperature was elevated to - 10 ° c ., and kept for 5 hours . then , it was lowered again to - 40 ° c . and dried under vacuum . the temperature of the vials was kept at - 20 ° c . during the initial stage ( up to 66 hours ) of drying . under vacuum , the temperature was elevated to 20 ° c . and kept for 5 hours to give a freeze - dried pharmaceutical preparation containing am - 833 . ten grams of powdered am - 833 were dissolved in 55 ml of 1n sodium hydroxide solution , and the ph was adjusted to 10 . 1 with 1m lactic acid , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 44 ° c . and dried under vacuum . the temperature of the vials was kept at - 20 ° c . during the initial stage ( up to 22 hours ) of drying . under vacuum , the temperature was elevated to 20 ° c . and kept for 26 hours , and it was further elevated to 40 ° c . and kept for 20 hours to give a freeze - dried pharmaceutical preparation containing am - 833 . five grams of powdered nflx were dissolved in 50 ml of 1m lactic acid , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing nflx . five grams of powdered nflx were dissolved in 15 ml of 1n hydrochloric acid solution , and the ph was adjusted to 4 . 6 with 1m sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a similar manner as example 1 to give a freeze - dried pharmaceutical preparation containing nflx . five grams of powdered nflx and 10 grams of glucose were dissolved in 15 ml of 1n hydrochloric acid solution and the ph was adjusted to 5 . 5 with 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing nflx . five grams of powdered oflx were dissolved in 25 ml of 1m lactic acid and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing oflx . five grams of cpfx were dissolved in 15 ml of 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 42 ° c . the temperature was elevated to - 10 ° c ., and kept for 2 hours . then , it was cooled again to - 40 ° c . and dried under vacuum . the temperature of the vials was kept at - 20 ° c . during the initial stage ( up to 21 hours ) of drying . subsequently , the temperature was elevated to 20 ° c . and kept for 65 hours under vacuum to give a freeze - dried pharmaceutical preparation containing cpfx . five grams of powdered cpfx were dissolved in 45 ml of 1n acetic acid solution , and diluted with a water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were refrigerated by cooling to - 42 ° c . and dried under vacuum in a manner similar to that of example 9 to give a freeze - dried pharmaceutical preparation containing cpfx . five grams of powdered cpfx were dissolved in distilled water for injection and dissolved in 100 ml of distilled water . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing cpfx . five grams of powdered enx were dissolved in 25 ml of 1m lactic acid , the ph was adjusted to 4 . 5 with 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were refrigerated by cooling to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing enx . five grams of powdered am - 1091 were dissolved in distilled water for injection and diluted up to 100 ml with the distilled water . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum . the temperature of the vials was kept at - 20 ° c . during the initial stage ( up to 5 hours ) of drying . subsequently , the temperature was elevated to 20 ° c . and kept for 63 hours for drying under vacuum to give a freeze - dried pharmaceutical preparation containing am - 1091 . five grams of powdered am - 1091 were dissolved in 25 ml of 1n sodium hydroxide solution , and diluted with distilled water for injection to 100 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . the temperature was elevated to - 10 ° c ., and kept for 5 hours . then , it was lowered again to - 40 ° c . and dried under vacuum . the temperature of the vials was kept at - 20 ° c . during the initial stage ( up to 6 hours ) of drying . subsequently , the temperature was elevated to 20 ° c . and kept for 21 hours for drying under vacuum to give a freeze - dried pharmaceutical preparation containing am - 1091 . one gram of powdered ny - 198 was dissolved in 20 ml of acetic acid and diluted with distilled water for injection to 50 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 14 to give a freeze - dried pharmaceutical preparation containing ny - 198 . one gram of powdered t - 3262 was dissolved in 20 ml of 1m lactic acid and diluted with distilled water for injection to 50 ml . this solution was filtered through a membrane filter ( pore size 0 . 22 μm ), and each 2 ml of the filtrate was filled into clean and sterilized vials . these vials were cooled to - 40 ° c . and dried under vacuum in a manner similar to that of example 1 to give a freeze - dried pharmaceutical preparation containing t - 3262 . the freeze - dried pharmaceutical preparations obtained were evaluated by a stability test , under light ( fluorescence lamp , 1 , 200 , 000 lux - hours ) and heat ( 50 ° c ., 3 months ) as compared with the solution prepared by using the same components . the results are shown in table 1 . these freeze - dried pharmaceutical preparations of the present invention have excellent properties , particularly with respect to stability as compared with those for the solutions . table 1______________________________________result of the stability tests of thefreeze - dried pharmaceutical preparationsof this invention and solutions lightexamples ( fluorescence lamp ) heat ( 50 ° c ., 3 months ) no . freeze - dried solution freeze - dried solution______________________________________ 1 no changes yellowish no changes yellowish 6 no changes slightly no changes no changes yellowish 8 no changes slightly no changes no changes yellowish12 no changes slightly no changes no changes yellowish13 no changes precipitate no changes no changes of light brown15 no changes slightly no changes no changes brown______________________________________
freeze - dried pharmaceutical preparation containing antibacterial quinolinecarboxylic acid derivatives are provided . these preparations are characterized by their stability against light and heat and have rapid solubility .