Europaisches Patentamt European Patent Office © Publication number: 0 200 508 Office europeen des brevets A2 © EUROPEAN PATENT APPLICATION © Application number: 86303170.4 © int. CIA A61K 9/70 , A61L 15/06 © Date of filing: 25.04.86 © Priority: 27.04.85 JP 91580/85 © Applicant: NITTO ELECTRIC INDUSTRIAL CO., 27.04.85 JP 91581/85 LTD. No. 1-2, Shimohozumi 1-chome Ibaraki-shi © Date of publication of application: Osaka(JP) 10.12.86 Bulletin 86/45 Applicant: SUNSTAR INC. 3-1 Asahi-cho © Designated Contracting States: Takatsuki-shi Osaka(JP) CH DE FR GB LI NL SE @ Inventor: Inoue, Yuichi Nitto Elec. Ind. Co. Ltd. 1-2 Shinohozumi 1-chome Ibaraki-shi Osaka(JP) Inventor: Horiuchi, Tetuo Nitto Elec. Ind. Co. Ltd. 1-2 Shinohozumi - 1-chome Ibaraki-shi Osaka(JP) Inventor: Hasegawa, Kenji c/o Sunstar Inc 3-1 Asahi-cho Takatsuki-shi Osaka(JP) Inventor: Nakashima, Koichi c/o Sunstar inc 3-1 Asahi-cho Takatsuki-shi Osaka(JP) Inventor: Ysuyoshi, Takashi c/o Sunstar inc 3-1 Asahi-cho Takatsuki-shi Osaka(JP) © Representative: Diamond, Bryan Clive Gee & Co. Chancery House Chancery Lane London WC2A 1QU(GB) © Adhesive oral and oral < bandages pharmaceutical preparations. 00 o © A polycarboxylic acid or anhydride, e.g. acrylic The bandage shows strong adhesion for a period IT)or or methacrylic acid polymer or maleic anhydride of at least 3 hours to the oral mucosa or teeth. polymer,polymer, is mixed with a vinyl acetate polymer pref- A topical drug can be incorporated in the adhe- Oerably erably of viscosity-average molecular weight of at sive bandage, to form an oral pharmaceutical prep- CMleast least 60,000, and optionally with a base capable of aration from which the drug is gradually released. neutralisingneutralising the acid or anhydride, e.g. a salt of a CL metal or a weak acid. The mixture in a mutual LUorganic organic or aqueous organic solvent is cast on a sheet base and dried and peeled off to form an oral bandage, which may include a soft film support. Rank Xerox This invention relates to an oral bandage that the administered drug or to provide protection by can be adhered to the oral mucosa to prevent a adhesion to the affected or injured part of the oral drug administered to the oral mucosa from running cavity. Therefore, it is required to have strong and out and to cover or protect the affected part of the long-lasting adhesion to the oral mucosa which oral mucosa, and to oral preparations comprising may be less adherable due to the administered such a bandage having incorporated therein a topi- drug or stomatorrhagia. Since both adhesive cal drug. strength and duration of adhesion of the aforesaid In the field of dental and oral surgery, various conventional preparations adhesive to the oral mu- topical preparations in the form of ointments or cosa are not so high as demanded for an oral solutions have hitherto been administered to the bandage, application of bases used in these prep- oral mucosa for prophylaxis and therapy of oral arations to an oral bandage can never satisfy the diseases, such as periodontal disease, stomatitis, above-described requirements of an oral bandage. etc. The most serious problem in administering The conventional adhesive tapes which are intend- drugs to the oral mucosa is that the drug runs ed to be applied to the skin cannot be, of course, away in a short time by salivary secretion or used as an oral bandage because they have no through eating or drinking, thereby failing to fully adhesion to a wet surface such as oral mucosa. exert its medical effects. An oral bandage is required to have not only On the other hand, protection of the affected strong and long-lasting adhesion to the oral mu- part in the oral cavity has scarcely been conducted cosa as described above but also softness suffi- because no effective oral bandage has been devel- dent to be adhered to any desired site of com- oped. As mentioned above, the continuous salivary plicated shape in the oral mucosa and, in addition, secretion and taking of foods and drinks constitute safety from worsening of the injury due to irritation. an insuperable barrier to the protection of the oral However, an oral bandage having such perfor- mucosa. mance characteristics has not yet been developed. In recent years, many proposals have been The present invention is intended to meet the made in an attempt to effectively administer a drug above-described situations. to the mucosa of the oral cavity, so as to overcome Accordingly, an object of this invention is to the above-described problems. Among them, pro- provide an oral bandage having high adhesive posals relevant to the present invention relate to strength for a prolonged period of time and soft- preparations adhesive to the oral mucosa, which ness with which to adhere to desired site of the contain water-soluble high-molecular substances as oral mucosa or teeth. an adhesive. When water-soluble high-molecular Another object of this invention is to provide an substances absorb a small amount of water, they oral preparation adhesive to the oral mucosa by become a viscous aqueous solution or gel having which an active ingredient can be surely and effec- adhesion, though varying in extent with their kind. tively administered to the oral mucosa. Making use of this property, various preparations According to the invention we provide an oral adhesive to the oral mucosa have been proposed, bandage comprising an adhesive film or a compos- including pastes as disclosed in Japanese Patent ite of such an adhesive film and a soft film support, Publication No. 27491/81, sponges as disclosed in said adhesive film comprising a mixture of a poly- Japanese Patent Publication No. 25211/81, tablets carboxylic acid and/or a polycarboxylic acid anhy- as disclosed in Japanese Patent Publication No. dride and a vinyl acetate polymer in a compatible 7605/83, sheets as disclosed in Japanese Patent state; and an oral preparation comprising such an Publication No. 16676/69 and Japanese Patent Ap- oral bandage having incorporated therein a topical plication (OPI) No. 186913/84 (the term "OPI" has drug. herein used means "unexamined published appli- The term "compatible state" as herein used cation"). means such a state that the polycarboxytic acid However, these conventional preparations only and/or polycarboxylic acid anhydride (hereinafter are intended to have enough adhesion to allow simply referred to as "polycarboxylic acids") and them to remain in position for a period of time the vinyl acetate polymer (hereinafter referred to as enough to administer the drug to the mucosa. In polyvinyl acetate) are uniformly dissolved in each other words, these preparations do not possess other without forming small individual regions due strong adhesion for an extended period of time as to phase separation. required for an oral bandage. On the contrary, an oral bandage is intended to prevent running-off of Water-soluble high-molecular compounds, such adhesion upon water absorption, such adhesion as polycarboxylic acids and polycarboxylic acid being substantially unchangeable even when im- anhydrides have per sea shape-retention property. mersed in water. Such a characteristic can first be When they absorb a small amount of water, they manifested when the polycarboxylic acids and exhibit strong adhesiveness but soon take up ex- polyvinyl acetate are in a compatible state, not cess water to cause reduction in viscosity and appearing when they are not in a compatible state. degradation, thus resulting in losing their adhesive- As described above, the mixture of the polycar- ness by being substantially dissolved in water. boxylic acids and polyvinyl acetate in a compatible Moreover, since polycarboxylic acids in a dissolved state exhibit characteristics unpredictable from state are acidic, they heavily irritate the sensitive those of a mixture in a phase-separated state. More injured part of the oral mucosa to cause worsening specifically, a film in a phase-separated state is of the condition. turbid, whereas a film in a compatible state has The present inventors have conducted exten- such a high transparency that no independent sive investigations on water-insolubilization of the small region is observed under an optical micro- above-described water-soluble high-molecular com- scope. Further, when immersed in water, the poly- pounds, such as polycarboxylic acids, polycarbo carboxylic acids is dissolved out from the film in a xylic acid anhydrides, etc., aiming at effective utili- phase-separated state, resulting in degradation as zation of these compounds exhibiting excellent ad- a whole; while the film in a compatible state only hesion upon absorption of water as an oral ban- undergoes uniform swelling with very little elution dage, while eliminating the above-described dis- of the polycarboxylic acids into water, which in- advantages, i.e., loss of adhesion due to over- dicates that the polycarboxylic acids is substan- absorption of water and irritation of the injured part. tially water-insolublized. The compatible state - As a result, it has now been found that polycarbox- (compatibility) of the polycarboxylic acids and poly- ylic acids and polyvinyl acetate are compatible with vinyl acetate can be determined by making use of each other, and mixing of these two components in insolubilization of the polycarboxylic acids. a compatible state substantially realizes water-in- When a basic substance capable of neutraliz- solubilization of the polycarboxylic acids without ing polycarboxylic acids is mixed with the above- impairing the strong adhesion upon water absorp- described compatible mixture, the state of its mix- tion. Therefore, even if such a compatible mixture ing has no substantial influence on the adhesion of the two components is shaped into a thin and property.