Patent Document:

the present inventors have confirmed that tranilast significantly suppressed proliferation of pterygium tissues in the in vitro test for inhibition of cell proliferation using pterygium tissue - derived cells . as a consequence , tranilast has been found to have a highly significant inhibitory effect on the proliferation of pterygium tissue - derived cells and is an extremely useful compound as an agent for inhibiting the progress of pterygium and postoperative recurrence of the same . pharmaceutical compositions which are useful as agents inhibiting the progress of pterygium and postoperative recurrence of the same in accordance with this invention can be prepared comprising as the active ingredient tranilast or a pharmaceutically acceptable salt thereof . various methods for the preparation of tranilast and salts thereof which are active ingredients are known , and these compounds can be readily prepared according to methods described in the literature and the like ( japanese patent application publication ( kokoku ) no . sho . 56 - 40710 ; ibid . no . sho . 57 - 36905 ; ibid . no . sho . 58 - 17186 ; ibid . no . sho . 58 - 48545 ; ibid . no . sho . 58 - 55138 ; ibid . no . sho . 58 - 55139 ; ibid . no . hei . 01 - 28013 ; ibid . no . hei . 01 - 50219 ; ibid . no . hei . 03 - 37539 etc .). as examples of pharmaceutically acceptable salts of tranilast , salts with inorganic bases such as a sodium salt and a potassium salt , salts formed with organic amines such as morpholine , piperazine , piperidine and pyrrolidine and salts formed with amino acids can be illustrated . the pharmaceutical compositions of the present invention can be employed in the practical treatment , of inhibiting the progress of pterygium by being administered orally , or preferably , topically as eyedrops , eye ointments and the like . for example , eyedrops can be formulated by dissolving tranilast or a pharmaceutically acceptable salt thereof together with a basic substance with heating in a proper quantity of sterilized water in which a surface active agent is dissolved , adding polyvinylpyrrolidone , and optionally adding appropriate pharmaceutical additives such as a preservative , a stabilizing agent , a buffer , an isotonicity , an antioxidant and a viscosity improver to dissolve completely . eye ointments can be appropriately formulated by using bases which are generally used in eye ointments . eye ointments can be also used as reversible thermally gelling water - base pharmaceutical compositions . when the pharmaceutical compositions of the present invention are employed in practical treatment , the dosage of tranilast or a pharmaceutically acceptable salt thereof as the active ingredient is appropriately decided depending on the age , degree of symptoms of each patient to be treated , therapeutic value and the like . the dosage should be fixed at an appropriate concentration to be curable . for example , in case of eyedrops , preferably a 0 . 001 - 2 weight % concentration of tramlast can be used . eyedrops are applied 1 to several times per day and applied at a dose of 1 to several droplets per time . the present invention is further illustrated in more detail by way of the following example . human pterygium tissues were cut into narrow strips . the strips were adhered to a culture plate and subcultured in dulbecco &# 39 ; s modified eagle &# 39 ; s medium ( dmem ) containing 10 % fetal calf serum ( fbs ) at 37 ° c . in an atmosphere of 5 % co 2 in air . at the point that cells were migrated and proliferated from the tissues , the medium was aspirated and cells were washed with phosphate - buffered saline ( pbs (-)) gently . then , the pbs (-) was aspirated , an aliquot of 0 . 25 % trypsin solution containing 0 . 02 % edta was added to the culture plate , and the morphology of cells was observed under phase - contrast microscopy . when cells were going to be round , an equal value of dmem containing 10 % fbs was added to the trypsin solution to stop the action of trypsin . attached cells were harvested from the plate by pipetting the medium using a slender pasteur pipette . the cell suspension was transferred into spit , then medium was added to the spit , and the cell suspension was mixed about 20 times vigorously by pipetting with a pasteur pipette and centrifuged at 100 - 110 xg for 1 minute . after the supernatant was discarded , fresh medium was added to the precipitate , and the pterygium - derived cell suspension was prepared by pipetting using a pasteur pipette . the suspension was further subcultured in dmem containing 10 % fbs to use for the experiment . tranilast was added to a 1 % aqueous sodium bicarbonate solution at a final concentration of 1 . 0 % and dissolved by warming at 70 ° c . the solution was sterilized with a millipore filter and diluted with dmem containing 10 % fbs to a final prescribed concentration . dmem medium ( 2 ml ) containing cells ( 2 × 10 4 cells ) and 10 % fbs was added to each well using a culture plate ( 6 - well ), and cultured . after 1 day , the medium was aspirated , dmem medium ( 2 ml ) containing various concentrations of tranilast and 10 % fbs was added to the plate , and cultured at 37 ° c . in an atmosphere of 5 % co 2 in air . after 2 days , the medium was aspirated , the cells were washed with pbs (-), and 1 ml of 0 . 25 % trypsin solution containing 0 . 02 % edta was added to the plate . after harvesting cells from the plate by pipetting using a pasteur pipette , the number of viable cells was counted under phase - contrast microscopy using a hemocytometer . mean and standard error values of each group were calculated . statistical analysis of significance was performed by a one - way analysis of variance and statistical significance was confirmed . thereafter , analysis of the significance between groups was performed by dunnett &# 39 ; s multiple test . as shown in fig1 tranilast significantly suppressed the proliferation of pterygium tissue - derived cells in a concentration - dependent manner . a pharmaceutical composition of the present invention comprising as the active ingredient tranilast has a marked inhibitory activity on proliferation of pterygium tissues and is suitable as an agent inhibiting progress of pterygium and postoperative recurrence of the same .

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