( a ) the solution ( a ) of the film base agent for preparing the pharmaceutical layer : 3 . 5 g of hydropropyl cellulose and 0 . 5 ml of macrogol - 400 ( polyethylene glycol ) were dissolved in 63 g of ethyl alcohol and 10 ml of distilled water containing 100 mg of dissolved predonisolone was added to the resulting solution . 0 . 5 g of hydroxypropyl cellulose , 0 . 25 ml of magrogol ( polyethylene glycol ) and 0 . 25 g of shellac were dissolved in 6 g of ethyl alcohol . ( c ) the solution ( c ) of the film base agent for preparing the intermediate layer : 3 . 5 g of hydroxypropyl cellulose and 0 . 5 ml of magrogol - 400 ( polyethylene glycol ) were dissolved in 63 g of ethyl alcohol . the film base agent solution ( a ) for producing the pharmaceutical agent layer ( a ) was first poured into the film molding frame ( i . e . teflon plate ) having 10 cm 2 of surface area , being placed in a horizontal position . after a drying step , the film base agent solution ( c ) for preparing the intermediate layer ( c ) was poured on the film containing the pharmaceutical agent and then , after it had dried , the film base agent solution ( b ) for preparing the poor water - soluble layer ( b ) was injected onto it . after a semi - drying step , the laminated film was stripped from the film molding frame . the stripped film was cured at 50 ° c . temperature for half a day . the film produced consisted of three layers and had a transparency and a soft flexibility . further , by almost the same operation , three laminated layer films having different combinations of compositions were obtained as set forth in table 1 . instead of the predonisolone in the film base agent of the pharmaceutical layer ( a ) shown in example [ 1 ], allantoin , i . e . 3 - ureido hydantoin ) was employed . the two laminated films having different combinations of the composition were obtained from the film base agent solution ( a ) containing the allantoin and the film base agent solution ( b ) producing the poor water - soluble layer ( b ) is set forth in table 2 . by using the film preparation in example [ 1 ], an elution test for the pharmaceutical component &# 34 ; predonisolone &# 34 ; was carried out . the test result is set forth in fig1 . product &# 34 ; vsp ( nf )&# 34 ; of toyama industry co ., ltd . standard grade : ntr - 5s . aq . dest . 1 , 000 ml 37 ° c . and a basket having 100 rpm rotational velocity . product &# 34 ; tas - 30 tc ii &# 34 ; of toyama industry co ., ltd . sampling amount : 10 ml and interval : 15 minutes . the film preparation obtained in example [ 1 ] was applied to a patient suffering from &# 34 ; after &# 34 ; type of an oral inflammatory disease . the film preparation is cut to a size slightly larger than the affected area so that the cut piece may contain from 2 to 16 mg of predonisolone and the cut piece was made to adhere onto the affected oral part . as a result , the film preparation showed favorable adhesive characteristics and it was not stripped off in the course of its therapeutical disposal . in all the examples of applying the invention , a rapid curing effect was recognized . further , in using the film preparation of the present invention , the affected part is protected with a soft film and a physical stimulus by the teeth or by food can be avoided . consequently , the pain which is caused by stress in this disease is greatly mitigated . as a comparison in this respect , a predonisolone tablet having 1 . 2 mm thickness was made to adhere over the affected part and this time there was a residual pain . table 1__________________________________________________________________________example no . [ 1 ]- 1 [ 1 ]- 2 [ 1 ]- 3 poor or poor or poor or pharma - difficult pharma - difficult pharma - difficult ceutical inter - water - ceutical inter - water - ceutical inter - water - agent mediate soluble agent mediate soluble agent mediate soluble layer layer layer layer layer layer layer layer layer__________________________________________________________________________predoni - 100 mg -- -- 100 mg -- -- 100 mg -- -- solonehydroxy - 3 . 5 g 3 . 5 g 0 . 5 g 3 . 5 g 2 . 5 g 0 . 5 g 3 . 5 g 2 . 5 g 0 . 5 gpropylcellulosehydroxy - -- -- -- -- -- -- -- -- -- propylmethyl - cellulosemethyl -- -- -- -- -- -- -- -- -- cellulosemacrogol 0 . 5 ml 0 . 5 ml 0 . 25 ml 0 . 5 ml 0 . 5 ml 0 . 25 ml 0 . 5 ml 0 . 5 ml 0 . 25 ml400shellac -- -- 0 . 25 g -- -- 0 . 25 g -- -- 0 . 5 gthe used 10 : 0 10 : 0 10 : 0solventethylalcohol : __________________________________________________________________________ [ 1 ]- 4 [ 1 ]- 5 poor or poor or pharma - difficult pharma - difficult ceutical inter - water - ceutical inter - water - agent mediate soluble agent mediate soluble layer layer layer layer layer layer__________________________________________________________________________ predoni - 100 mg -- -- 100 mg -- -- solone hydroxy - 2 . 0 g 3 . 5 g 0 . 3 g 2 . 0 g 3 . 5 g 0 . 3 g propyl cellulose hydroxy - 1 . 5 g -- 0 . 2 g -- -- 0 . 2 g propyl methyl - cellulose methyl -- -- -- 1 . 5 g -- -- cellulose macrogol 0 . 6 ml 0 . 5 ml 0 . 3 ml 0 . 6 ml 0 . 5 ml 0 . 3 ml 400 shellac -- -- 0 . 25 g -- -- 0 . 25 g the used 8 . 0 : 2 . 0 7 . 0 : 3 . 0 solvent ethyl alcohol : __________________________________________________________________________ table 2__________________________________________________________________________ [ 2 ]- 1 [ 2 ]- 2 [ 2 ]- 3 poor or poor or poor or difficult difficult difficult pharmaceutical water - soluble pharmaceutical water - soluble pharmaceutical water - soluble agent layer layer agent layer layer agent layer layer__________________________________________________________________________allantion 2 . 0 g 2 . 0 g 2 . 0 ghydroxypropyl cellulose 3 . 5 g 0 . 75 g 3 . 5 g 0 . 5 g 3 . 5 g 0 . 25 gmacrogol 400 1 . 0 ml 0 . 25 ml 1 . 0 ml 0 . 25 ml 1 . 0 ml 0 . 25 mlshellac -- 0 . 25 g -- 0 . 5 g -- 0 . 75 gthe used solvent ethyl alcohol ethyl alcohol ethyl alcohol__________________________________________________________________________ the mucous membrane - adhering film preparation of the present invention is a complex film preparation which consists of a pharmaceutical layer and poor water - soluble layer , or , a pharmaceutical layer , an intermediate layer and a poor water - soluble layer . consequently , the pharmaceutical layer strongly adheres to the diseased part by absorbing moisture content and then , the pharmaceutical layer becomes wet and swollen . subsequently , the pharmaceutical agent is gradually dissolved in the diseased part in the course of long hours and the pharmaceutical agent can then be almost homogeneously eluted . on the other hand , the poor water - soluble layer has poor water solubility and consequently , the pharmaceutical component of the pharmaceutical layer is not eluted and it can be retained in a buccal cavity or the like for long hours without giving a feeling of contacting an extraneous material . as heretofore mentioned , the film preparation indicates a superior effect which is entirely different from that found in a conventional pharmaceutical preparation . ( 1 ) the film preparation can be used for therapeutical purposes on a local diseased part or for the whole body . ( 2 ) because of the gradual discharge of the pharmaceutical component , the useful hours are long and less stimulation is given to the diseased part . ( 3 ) the film preparation can be used for the musous membrane or the diseased part wetted with a diffused liquid or a secreted liquid . ( 4 ) the film preparation can be cut to any size and thereby a predetermined amount of the pharmaceutical agent may be used . ( 5 ) the film preparation protects the diseased part from physical harm . ( 6 ) many different pharmaceutical agents can be used for the film preparation . ( 9 ) even if the film base agent is swallowed , it is not absorbed in the walls of the internal organs . it is to be observed therefore that the present invention provides a novel film preparation for applying to the mucous membrane and to the process of producing the preparation .
a mucous membrane - adhering film preparation wherein the film consists of two layers . one layer of the film consists of the pharmaceutical agents and water - soluble high polymer material . the other layer of the film material consists of poor water - soluble agents . the pharmaceutical agent and water - soluble high polymer material layer first layer and the poor water - soluble agents second layer are separately prepared in solvents . the first solution is coated on a base plate having a favorable releasing nature , and , by removing the solvent , the film is produced on the base plate , the second solvent is then coated on the first layer and by removing the solvent , the desired film having one poor water - soluble surface is produced .