JPH062671B2 - Oral formulation - Google Patents

Description

TECHNICAL FIELD The present invention relates to an intraoral preparation which is applied to a moist mucous membrane or a tooth surface in the oral cavity and exerts a local effect on an application site for a long time.

[Conventional technology]

Conventionally, various drugs have been administered as ointments and liquids for oral diseases such as alveolar pyorrhea and inflammation.
In addition to these local therapeutic agents, focusing on the fact that the mucosal surface absorbs the drug relatively well compared to the outer skin,
It has been attempted to administer systemic drugs such as hormones, which are difficult to be absorbed by oral administration, through the oral mucosa. The biggest obstacle to the administration of a drug through the oral mucosa is that the drug is washed away in a short time due to the secretion of saliva and the eating and drinking, and it is difficult to exert a sufficient drug effect. is there.

Further, it has been hardly performed to cover and protect the damaged part in the oral cavity because there is no effective oral bandage, but saliva is always secreted in the oral cavity as described above, and food and drink are also Therefore, there is a major obstacle to realizing the coating protection.

Recently, paste buccal tablets (Japanese Patent Publication No. 54-38168) and adhesive tablets (Japanese Patent Publication No. 57-29448) have been used as preparations for overcoming these obstacles and enhancing the retention of the drug on the oral mucosa. , JP-A-56-100714
No.) and film preparations (JP-A-60-11663).
No. 0) etc. have been proposed.

[Problems to be solved by the invention]

However, these oral mucosa-adhesive preparations do not have long-term adhesion persistence, and do not adhere well particularly when bleeding from an oral injury site or when the amount of salivary glands is large,
There is a drawback that the coating protection property for those parts is poor. In addition, it has been proposed that a topical drug such as a bactericidal agent or a breath odor remover is contained in the above-mentioned preparation for oral mucosa adhesion (base), and thereby a local effect is obtained. If it is contained in the composition, the stability of the drug is impaired due to the interaction between the drug and the base, and the release property is impaired (not released well from the base). There is a problem with the conversion.

The present invention has been made in view of such circumstances, and even when bleeding from an injured site in the oral cavity, long-term adhesion persistence is exhibited even when saliva secretion is large, and stability of the contained drug and An object thereof is to provide an oral preparation having good release properties.

[Means for solving problems]

In order to achieve the above object, the oral preparation of the present invention,
An oral bandage consisting of an integrated body of a film-like adherent and a flexible film-like support, wherein the film-like adherent is a compatible state of at least one of a polycarboxylic acid and a polycarboxylic acid anhydride and a vinyl acetate polymer. It is composed of a flexible film-like material, and the above-mentioned flexible film-like support comprises a water-absorbing polymer substance containing a local drug dispersed therein.

That is, the inventors of the present invention configured a film-like adherent from a film composed of a compatible solution of at least one of a polycarboxylic acid and a polycarboxylic anhydride and a vinyl acetate polymer so that the film-like adherent can adhere to the oral mucosa for a long time. We have already applied for a patent (Japanese Patent Application No. 60-915).
No. 80 (Japanese Patent Laid-Open No. 61-249472), Japanese Patent Application No. 60-
91581 (JP-A-61-249473). Then, as a result of further research, a flexible film-like support which is integrated with the film-like adherent and supports the film-like adherent, contains a topical drug-containing water-absorbing polymer substance in a dispersed manner, Furthermore, the adhesiveness to the mucous membrane in the oral cavity is improved, and it becomes possible to apply it even when bleeding from the damaged site in the oral cavity and when the saliva secretion is large, and at the same time, the topical drug is The inventors have found that the present invention is protected and stable, and that the drug is gradually released to maintain the local effect for a long period of time, and thus the present invention has been reached.

To explain this in more detail, water-soluble polymeric substances such as polycarboxylic acid and polycarboxylic acid anhydride have a shape-retaining property by themselves, and exhibit strong adhesiveness when a small amount of water is absorbed. However, it immediately becomes an excessively water-absorbed state, the viscosity is lowered, and it disintegrates to become a state of being substantially dissolved in water, and the adhesiveness is lost.

The present inventors take advantage of the strong adhesive force of water-soluble polymer substances such as polycarboxylic acid and polycarboxylic acid anhydride at the time of such water absorption, and effectively utilize this for oral preparations. A series of studies have been repeated with the aim of improving the loss of adhesion during a certain amount of excessive water absorption. As a result, the polycarboxylic acid and polycarboxylic acid anhydride are compatible with the vinyl acetate polymer, and when both are made compatible, the polycarboxylic acid and polycarboxylic acid anhydride are substantially insolubilized in water. It is realized in an enhanced state without impairing the strong adhesiveness at the time of absorbing water, and even if the compatibilized material of both is formed into a thin flexible film, it does not collapse by absorbing water in a wet state and has a strong adhesive force for a long time. I found that it started to express. As mentioned above, a patent application has already been made in this regard. And
As a result of continued research after that, the above-mentioned polycarboxylic acids and vinyl acetate polymer are dispersed in a flexible film-like support supporting a special film in which the topical drug-containing water-absorbing polymer substance is dispersed and contained. By doing so, the effect of further improving the adhesive force to the mucous membrane in the oral cavity can be obtained, and even if the bleeding from the damaged site in the oral cavity is caused by this, the saliva secretion is large. Even if it adheres strongly, it becomes possible to realize long-term coating protection, and at the same time, by gradually releasing the topical drug from the support into the oral cavity, the local effect of the drug is exhibited for a long time. It came to this invention by discovering that it came to be.

At least one of the above-mentioned polycarboxylic acid and polycarboxylic anhydride (hereinafter, these are referred to as “polycarboxylic acids”).
And a vinyl acetate polymer are compatible with each other, the flexible film has no adhesive property when dried.
It has an epoch-making property that it exhibits strong adhesiveness when absorbing water and its state hardly changes even when immersed in water.

In the present invention, the above film is a film-like adherent for an oral preparation. The epoch-making characteristics as described above are exhibited only when the polycarboxylic acid and the vinyl acetate polymer are in a compatible state, and do not appear when they are not in a compatible state.

The term "compatible state" as used herein means a state in which polycarboxylic acids and a vinyl acetate polymer or the like are uniformly dissolved without phase-separating to form independent small regions. When the polycarboxylic acids and the vinyl acetate polymer are in a compatible state, they exhibit properties that cannot be predicted from the properties of the mixture in the phase-separated state. That is, in the mixture of polycarboxylic acids and vinyl acetate polymer, the phase-separated film becomes cloudy and the compatible film becomes highly transparent. However, in the oral preparation of the present invention, in some cases, salts for neutralizing the polycarboxylic acids are contained in the film-like adherent, and in such a case, the polycarboxylic acids are Even if the vinyl acetate polymer is in a compatible state, if the salts are in a coarse mixed state, the film becomes cloudy. Therefore, it may not always be possible to determine the mixed state of the polycarboxylic acid and the vinyl acetate polymer by visual observation or observation with an optical microscope.

However, when the polycarboxylic acids and the vinyl acetate polymer are in a compatible state, the water solubility of the polycarboxylic acids, which should be water-soluble, is significantly limited, and even if the polycarboxylic acids are immersed in water for a considerably long time, they are homogeneous. It swells and does not collapse. This property is observed with and without the neutralizing salt. Utilizing this property, the compatibility of polycarboxylic acids and vinyl acetate polymer can be investigated. That is, in the present invention, the compatibility state of the polycarboxylic acid and the vinyl acetate polymer is to be investigated from the elution amount of the polycarboxylic acid, and the compatibility state in the present invention,
Specifically, it refers to a mixed state in which the dissolution rate determined by the following dissolution rate measurement method is 50% by weight (hereinafter abbreviated as "%") or less.

<Method of measuring elution rate> A film (film-like adherent) composed of polycarboxylic acids, a vinyl acetate polymer and a salt having a neutralizing action is placed at 0 ° C.
Grind and weigh as follows. This is placed in a mesh bag and immersed in purified water at 20 ° C., which is 300 times or more the weight of the adherent, in a stationary state for 1 hour, and then the adherent is taken out together with the bag. The amount of the polycarboxylic acids eluted in the purified water by this operation is determined from the weight loss of the adherent due to immersion. The dissolution rate is calculated by dividing this by the blending amount of polycarboxylic acids in the film.

Examples of the flexible film-like support which is integrated with a flexible film (film-like adherent) in which the polycarboxylic acids and the vinyl acetate polymer are in a compatible state and supports the film include polyethylene and acetic acid. Vinyl resin,
Examples thereof include plastic films made of ethylene-vinyl acetate copolymer, polyvinyl chloride, polyurethane, etc., laminated films made of cloth or paper and plastic film, and the like.
Above all, it is preferable to use polyethylene, vinyl acetate resin, ethylene-vinyl acetate copolymer, or other plastic film from the viewpoints of safety and usability. It is preferable to use such a flexible film-shaped support having a thickness of 10 to 100 μm from the viewpoints of handling and not giving a feeling of foreign matter during use. The integrated product with and is preferably regulated in thickness within the range of 30 to 150 μm. That is, the thickness is 3
If it is less than 0 μm, the handling and operability will be poor, and
This is because if it exceeds m, it tends to give a feeling of foreign matter during use.

In this case, in order to integrate the above-mentioned flexible film-like support with the film-like adherent, it can be carried out by a usual method such as thermocompression bonding or using an adhesive. In addition, by casting the composition used for the production of the film-like adherent on a flexible film-like support, and simultaneously performing the production of the film-like adherent and the laminating with the flexible film-like support. Can also be manufactured. In the latter case, there is an advantage that the thermocompression bonding and the bonding work are unnecessary and the manufacturing can be simplified.

Examples of the water-absorbing polymer substance in the topical drug-containing water-absorbing polymer substance contained in the flexible film-like support include starch acrylate graft polymer (starch type), carboxymethyl cellulose crosslinked body (cellulose type) and Examples thereof include vinyl alcohol acrylate copolymers, polyacrylonitrile hydrolysates, crosslinked polyacrylates, and synthetic polymer-based ones such as modified polyvinyl alcohol. These may be used alone or in combination of two or more kinds without any problem.

Examples of the topical drug to be contained in the water-absorbing polymer substance include bactericides (cetylpyridinium chloride, decalinium chloride, metronidazole, chlorhexidine, tetracycline, minocycline, penicillin, doxycycline, oxytetracycline, cefatrizine,
Nystatin, clindamycin, fradiomycin sulfate and salts thereof, breath freshener (l-menthol,
Copper chlorophyllin sodium, lemon oil, ascorbic acid, cetylpyridinium chloride, decalinium chloride, etc.),
Oropharyngeal drugs (cetylpyridinium chloride, decalinium chloride, water-soluble azulene, dipotassium glycyrrhizinate, powdered chrysanthemum, chlorpheniramine maleate, popidone iodine, etc.) and the like can be mentioned. These topical agents are transferred and released out of the support by the water such as saliva flowing from the side peripheral surface of the film-like support and the like, to exert a local effect. Incorporation of such a topical drug in the water-absorbing polymer substance makes the water-absorbing high-molecular substance dissolved in water, an acidic solution, an alkaline solution, a water-alcohol solution, an alcohol, a polyhydric alcohol, or the like in which the drug is dissolved. It can be carried out by adding a molecular substance to absorb water and then drying. Further, in some cases, the obtained water-absorbing polymer substance containing a local drug may be coated with a water-soluble polymer substance, an anti-salivational polymer substance, an enteric polymer substance or the like. Examples of the water-soluble polymer substance include hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, carboxyvinyl polymer, sodium carboxymethyl cellulose, hydroxyethyl cellulose, pullulan and the like. Further, as the enteric polymer substance, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, carboxymethylethylcellulose, hydroxypropylmethylcellulose acetate succinate, methacrylic acid / methyl methacrylate copolymer (Eudragit L10
0, Eudragit S100, manufactured by Rohm Fuama)
Examples of the anti-salivational polymer substance include dimethylaminoethyl methacrylate / methyl methacrylate copolymer (Eudragit E100, manufactured by Rohm Pharma Co., Ltd.),
Examples of the water-insoluble polymer include ethyl cellulose, ethyl methacrylate / trimethylammonium methacrylic acid trimethylammonium copolymer (Eudragit RS10
No. 0, manufactured by Rohm Pharma Co., Ltd.) and ethyl methacrylic acid methyl acrylate copolymer (Eudragit E10D, manufactured by Rohm Pharma Co.).

It is preferable that such a topical drug-containing water-absorbent polymer substance is uniformly dispersed in a support made of the above-mentioned flexible film, and it is necessary to disperse and contain it in the film so as to be less than 20%. is there. Particularly preferred is 5
It is within the range of 20%, and within this range, the extension of the adhesion time and the hemostatic effect can be well exhibited. Further, 5 to 15% is preferable. Within this range, it does not peel off even after 5 hours from application and a good hemostatic effect is observed.

The oral preparation of the present invention, as described above, is a film-like adherent which is a flexible film exhibiting adhesiveness only when absorbing water without exhibiting adhesiveness when dried, and the film-like adherent is dried. Since it does not have adhesiveness when it is in use, it can be stored as it is without any special storage mode, and when it is used, it simply presses against the mucous membrane in the oral cavity to absorb saliva on the mucous membrane and moisture in the mucous membrane and quickly develop adhesiveness Strongly adheres to mucous membranes. Therefore, it strongly adheres to the oral disease site or damaged site where it is difficult to adhere due to the administered drug or bleeding, etc., and exerts a drug outflow and a wound covering protection effect. This coating protection effect is enhanced by the action of the drug-containing water-absorbing polymer substance in the flexible film-like support that supports the film-like adherent, and the local content of the drug-containing water-absorbing polymer substance is increased. Due to the action of the sexual drug, the local effect will be sustained for a long period of time,
This is a great feature of the present invention.

In this case, it is conceivable that the polycarboxylic acids will stimulate the damaged part and the like at the initial stage of applying the oral preparation to the mucous membrane. In such a case, as described above, it is preferable to add a salt having a neutralizing action to polycarboxylic acids to the film-like adhered body composed of the above-mentioned flexible film. By doing so, the polycarboxylic acids are neutralized, so that irritation is not applied to the damaged site and no problem occurs even if the adhesion is continued for a long time.

The above-mentioned long-term adhesion persistence in the oral preparation of the present invention is, as described above, that the polycarboxylic acid and the vinyl acetate polymer are in a compatible state in the film-like adherent, and it is integrated with it. This is realized by dispersing and containing a local drug-containing water-absorbing polymer substance in a softened flexible film-like support.

Although the mechanism of generation of this adhesion sustainability is not clear, under compatible conditions, polycarboxylic acids provide adhesion to wet mucous membranes, vinyl acetate polymer imparts water resistance, and water-absorbing polymer substances form film. Films that appropriately absorb water that permeates into the film-like adherent from the side peripheral surface of the substrate to exert an appropriate water supply action on polycarboxylic acids, and these are well coordinated to develop long-term adhesion sustainability. it is conceivable that.

Incidentally, the salts having a neutralizing effect on polycarboxylic acids, the mixed state does not affect the adhesiveness,
The characteristics slightly affect the adhesion and the like. For example, polyvalent metal salts such as zinc oxide and calcium oxide function to reduce adhesion and increase water resistance, but monovalent metal salts such as sodium acetate and sodium hydroxide and triethanolamine. The monovalent base acts to increase adhesion and reduce water resistance.

Thus, the oral preparation of the present invention has a strong adhesive force to the mucous membrane of the oral cavity, and therefore exhibits a long-term coating protective effect on the site of oral disease and at the same time, the local effect of the topical drug. Can be maintained for a long time. In particular, sufficient coating protection can be performed even on a site where there is bleeding in an oral cavity injury site and also on a site where a large amount of saliva is secreted.

Further, the film-like adherent in the oral preparation of the present invention comprises a substantially water-insoluble flexible film in which polycarboxylic acids and a vinyl acetate polymer are in a compatible state, and is simply a water-soluble polymer substance. Since it is not used as it is, it exhibits long-term adhesion persistence in a very thin state. That is, when the water-soluble polymer substance is used as it is, if it is made too thin, it will not be thinned because it will be rapidly dissolved by saliva in a short time and the adhesive property will be rapidly lost. Will have a thickness of. However, in such a case, the feeling of foreign matter during use is increased, and at the same time, the flexibility of the oral preparation is impaired. Since the film-like adherent of the oral preparation of the present invention exhibits a strong adhesive force for a long time in a very thin state, it is not necessary to increase the thickness, and a feeling of foreign matter due to an excessive thickness is not felt. As described above, the oral preparation of the present invention is composed of a film-like adherent made of a thin and flexible film, and thus is soft and thin as a whole. Therefore, when it is used, it can be smoothly deformed along the mucous membrane in the oral cavity and easily attached by simply pressing it lightly, and it has an advantage that it does not give a foreign body sensation.

The oral preparation of the present invention can be produced, for example, as follows. That is, a polycarboxylic acid and a vinyl acetate polymer are dissolved in a common solvent for both, and in some cases, a salt having a neutralizing effect on the polycarboxylic acid is further mixed and mixed to form a uniform solution. to make. On the other hand, a film-like support in which a water-absorbing polymer substance is added to a solution in which a topical drug is dissolved to absorb the drug and then dried to prepare a water-absorbing polymer substance containing a local drug and which is dispersed and contained. Make a component solution of. Next, the obtained topical drug-containing water-absorbent polymer substance was added to the component solution of the film-like support, and filmed by a conventional method to obtain a flexible solution containing the topical drug-containing water-absorbent polymer substance dispersed therein. To make a simple film-like support. Then, an oral preparation can be produced by casting and drying a uniform solution of the above-mentioned polycarboxylic acid and vinyl acetate polymer on the flexible film-like support. In addition, a uniform solution of the above polycarboxylic acids and vinyl acetate polymer is cast.
It may be dried to form a film-like adhered body, which may be integrally manufactured by thermocompression bonding with the film-like support containing the topical drug-containing water-absorbing polymer substance obtained as described above. it can. According to the former, there is an advantage that a very thin oral preparation can be easily manufactured.

Representative examples of the above polycarboxylic acids include acrylic acid polymers, methacrylic acid polymers, and maleic anhydride polymers, which can be used alone or in combination. Specific examples of the acrylic acid polymer include acrylic acid homopolymers, acrylates such as butyl acrylate and 2-ethylhexyl acrylate, and
Examples thereof include copolymers with methacrylic acid esters such as methyl methacrylate and vinyl monomers such as vinyl acetate, and copolymers such as carboxyvinyl polymer. Further, specific examples of the methacrylic acid polymer include, in addition to the methacrylic acid homopolymer, the same copolymers as in the case of the acrylic acid polymer, and specific examples of the maleic anhydride polymer include methyl vinyl ether. And the like. It goes without saying that the compounds exemplified in the above specific examples can be used not only individually but also as a mixture. In these polycarboxylic acids, it is effective that the polycarboxylic acid contains 20% or more of —COOH groups and the polycarboxylic acid anhydride contains 16% or more of —CO—O—CO— groups. It is preferable above.

Further, when exemplifying a typical vinyl acetate polymer,
Examples thereof include vinyl acetate homopolymers, as well as copolymers of vinyl monomers such as acrylic acid esters and vinyl acetate, and partially saponified products obtained by partially saponifying vinyl acetate homopolymers. These can be used alone or in combination. Moreover, it is preferable that these have an average molecular weight (viscosity average molecular weight) of 60,000 or more.
If the average molecular weight of less than 60,000 is used, the water resistance of the above film-like adherent is lowered, and it is difficult to obtain the desired effect.

Salts having a neutralizing effect on polycarboxylic acids,
Not only a salt but also a base is included, and typical examples thereof include a salt of a metal with a weak acid, a metal oxide, a metal hydroxide, an amine and the like and a mixture thereof. Specific examples of salts of metals and weak acids include sodium, potassium,
Examples thereof include salts of calcium, magnesium and the like with carboxylic acids such as acetic acid, lactic acid and citric acid, and specific examples of metal oxides include zinc oxide, calcium oxide and magnesium oxide. Specific examples of metal hydroxides include sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide and the like, and specific examples of amines include triethanolamine, diisopropanolamine and the like. To be The compounds exemplified in the above specific examples can be used alone or in combination. The preferable blending amount of such salts greatly varies depending on the type of salt or base. When a polyvalent metal salt is used, the amount of the polycarboxylic acid in the film-like adherent is 0.2 to
It is preferable to add 0.8 equivalent, and if the amount is less than 0.2, the effect of reducing irritation to the damaged site (damaged mucous membrane) will be insufficient, and if it exceeds 0.8 equivalent, sufficient adhesion persistence will be difficult to obtain. . Further, when using a monovalent metal salt or a monovalent base, with respect to the polycarboxylic acids in the film-like adherent, it is preferable to add 0.03 to 0.2 head amount, and the amount is less than 0.03 equivalent. And the effect of reducing irritation to the damaged part becomes insufficient, and if it exceeds 0.2 equivalent, the water resistance of the film-like adhered material is lowered and it becomes difficult to obtain sufficient adhesive strength.

The common solvent for the polycarboxylic acids and the vinyl acetate polymer is a lower alcohol such as methanol or ethanol, and a mixture thereof with an organic solvent such as soluble acetone or ethyl acetate, the lower alcohol being the main component. Examples thereof include those described above, or the above mixture or a mixture obtained by further adding water to a lower alcohol. Regarding the above-mentioned solvent, it is preferable to limit the content of the organic solvent such as acetone and ethyl acetate to 30% or less. This is because if it exceeds 30%, it becomes difficult to dissolve the polycarboxylic acids. With regard to the above solvents, it is preferable to limit the content of water to 30% or less. This is because if the water content exceeds 30%, it tends to be difficult to dissolve the vinyl acetate polymer.

In the case of producing an oral preparation as described above,
The mixing ratio of the polycarboxylic acid and the vinyl acetate polymer is
It is preferable to regulate so that the A value obtained by the following equation is within the range of 15 to 55.

As the A value increases, the adhesive force of the film-like adherent to the mucous membrane increases, but the sticking durability tends to decrease. Conversely, the smaller the A value, the lower the adhesive force,
The adhesion persistence tends to increase. When the A value is less than 15, it becomes difficult to obtain sufficient adhesive force, and when it exceeds 55, it becomes difficult to obtain sufficient adhesion durability. Therefore, it is preferable to regulate the mixing ratio of the polycarboxylic acid and the vinyl acetate polymer so that the A value is within the range of 15 to 55. The case where polyacrylic acid is used as the polycarboxylic acid will be described as an example. The ratio of the polyacrylic acid in the film-like adherent is 24 to 24%.
When it is in the range of 88%, the A value falls within the above range, and a preferable result can be obtained.

Further, when the above-mentioned polycarboxylic acids and vinyl acetate polymer are dissolved in a common solvent, it is necessary to take care so that both are sufficiently dissolved. In this case, the concentration of the polymeric substance such as polycarboxylic acid and vinyl acetate polymer is not particularly limited, but if the concentration of the polymeric substance becomes too high, the solution viscosity becomes large, and the casting film is Since it tends to be difficult to form the polymer, it is preferable that the concentration of the polymer substance does not exceed 40%.

A solution prepared by dissolving polycarboxylic acids and vinyl acetate polymer and further adding a salt for neutralization, if necessary, is cast into a dry film, and is formed into a suitable film such as polyethylene laminated paper which has been subjected to release treatment. After casting the above solution on the surface, it can be dried by using a high-temperature air bath such as a dryer or a drying tower to form a film. In this case, it may be integrated by thermocompression bonding with a flexible film-shaped support containing the topical drug-containing water-absorbing polymer substance dispersed and obtained by the method described above. Done. The solution of polycarboxylic acids and a vinyl acetate polymer can be formed into a film-like adhered material by using the flexible film-like adhered material instead of the polyethylene laminated paper. In this case, at the same time when the film-like adherent is formed, the film-like adherent and the flexible film-like support are integrated with each other, and the former thermocompression bonding work can be eliminated. Like As described above, the film-like adhered product of the solution of the polycarboxylic acid and the vinyl acetate polymer can be prepared according to two kinds of measures. However, in any case, the appropriate drying time or drying temperature generally varies from 60 ° C. to 12 ° C., though it varies somewhat depending on the composition of the common solvent, the solid content concentration in the solution, the casting thickness, and the like.
It is preferable to dry at a temperature of 0 ° C. for about 1 to 20 minutes.

In addition, it is free to mix the film-like adherent or the film-like support of the oral preparation of the present invention with a colorant, a flavor, a softening agent, etc. within a range that does not hinder the adherence. For example, when both the adherent and the support are colorless, blending a colorant into one of the adherents and the support provides the advantage that the front and back of the preparation are clear and easy to use.

As described above, the oral preparation of the present invention is a film in which a topical drug-containing water-absorbing polymer substance is dispersed and contained in a film-like adherent composed of a compatible material of a polycarboxylic acid and a vinyl acetate polymer. Since it is configured by integrating a sheet-like support and is highly flexible as a whole, when it is stuck in the oral cavity, it absorbs moisture in the oral cavity and is further softened. Therefore, it easily fits to any part of the oral cavity (including the tooth surface), and exhibits strong adhesive force and long-lasting adhesive force. In particular, the oral preparation of the present invention has a topical drug-containing water-absorbing polymer substance dispersedly contained in a flexible film-like support, so that the adhesive force to the oral mucosa is remarkably improved, and the oral lesion site is damaged. Therefore, it can be applied to areas such as those where there is bleeding, and it is possible to achieve long-term coating protection, and at the same time, keep the topical drug covered and protected with the above polymer substance. Therefore, the drug is gradually released, and the local effect can be sustained for a long period of time. Moreover, the interaction between the drug and the base material does not occur.

〔The invention's effect〕

Since the oral preparation of the present invention is configured as described above, the adhesiveness to the oral mucosa is remarkably improved, and even for a damaged site in a bleeding state, a site with a large saliva secretion amount is also used. Adheres well and can realize long-term coating protection, while at the same time exhibiting a long-term local effect of the topical drug. Moreover, the above-mentioned oral preparation is flexible and deforms and adheres along the membrane surface of the mucous membrane of the oral cavity by simply pressing it at the time of use, and can be applied to any location in the oral cavity and is extremely practical.

Next, examples will be described together with comparative examples.

Example 1 Carboxyvinyl polymers were used as polycarboxylic acids, and 4.7 parts by weight (hereinafter abbreviated as “part”) and 4.7 parts of vinyl acetate resin (1500) were added to 90 parts of methanol, which is a common solvent for both. Then, 0.6 part of diisopropanolamine was added and mixed and dissolved to form a uniform solution. This solution was cast on a polyethylene-laminated paper which had been subjected to a release treatment, and dried in an oven at 80 ° C. for 8 minutes to form a film-like adherent having a thickness of 40 μm.

On the other hand, separately from this, cetylpyridinium chloride (CPC)
10 parts was dissolved in 200 parts of water, and 40 parts of a water-absorbing polymer substance composed of a vinyl alcohol acrylate copolymer was added thereto to absorb CPC and water. Then, 80 ℃
To remove water to produce a water-absorbing polymer containing CPC. Then, the obtained product was added to a solution prepared by dissolving 300 parts of vinyl acetate resin in 1200 parts of toluene and stirred as uniformly as possible to prepare a film-shaped support by a conventional method.

The film-like support thus obtained and the film-like adherent obtained as described above were thermocompression-bonded at 100 ° C. to obtain the target oral preparation.

When the obtained oral preparation was applied to the oral cavity of a patient with severe bad breath, the effect of eliminating or reducing bad breath was observed.

Example 2 The CPC-containing water-absorbing polymer substance obtained in Example 1 was spray-coated with a 2% strength hydroxypropylcellulose ethanol solution. Otherwise in the same manner as in Example 1, an oral preparation was obtained. When the obtained oral preparation was applied to the oral cavity of a patient with severe bad breath, it was confirmed that the disappearance of bad breath continued for a long time.

Example 3 The following raw materials were prepared in the proportions shown below.

Carboxy vinyl polymer: 3.4 parts Vinyl acetate resin (1000): 8.4 〃 Citric acid 3Na: 0.2 〃 Methanol: 71.0 〃 Purified water: 17.0 〃 Mix the raw materials as above and mix them to make a uniform mixture. A solution was obtained. Then, this solution was cast on polyethylene laminated paper and dried in a dryer at 80 ° C. for 15 minutes to obtain a film-like adherent having a thickness of 80 μm.

On the other hand, separately from the above, 2 parts of azulene is dissolved in 80 parts of water, and 18 parts of a water-absorbing polymer substance composed of a crosslinked polyacrylic acid salt is added thereto to absorb azulene and water, and then dried at 80 ° C. Then, water was removed to obtain a water-absorbent polymer substance containing azulene.

Next, this was added to a solution of 180 parts of an ethylene-vinyl acetate copolymer (vinyl acetate content 40%) dissolved in 540 parts of toluene, and the mixture was stirred as uniformly as possible to prepare a film-shaped support by a conventional method. After this, an oral preparation was obtained in the same manner as in Example 1.

When the obtained buccal preparation was applied to the oral cavity of a patient with swollen oral cavity and throat, a reduction in swelling of the oral cavity and throat was observed.

Example 4 In the same manner as in Example 3, a water-absorbing polymer substance containing azulene dispersed therein was produced, and a 1% concentration of methyl methacrylate-trimethylammonium methacrylic acid ethyl methacrylate copolymer (Eudragit SR100, Rohm Pharma) was prepared. A methylene chloride solution (manufactured by the company) was sprayed and coated. After this, an oral preparation was obtained in the same manner as in Example 3.

When the obtained oral preparation was applied to the oral cavity of a patient with swollen oropharynx as in Example 3, the effect of reducing the swollen oropharynx was observed over a long period of time.

Comparative Example 1 The use of the water-absorbing polymer material containing CPC was discontinued. Otherwise in the same manner as in Example 1, an oral preparation was obtained.

Comparative Example 2 A film-like adherent was prepared in the same manner as in Example 1. Separately, a solution of 10 parts of CPC dissolved in a small amount of methanol was prepared separately, and this was added to a solution of vinyl acetate resin and toluene in the same manner as in Example 1 to prepare a film-shaped support. After that, both were thermocompression-bonded in the same manner as in Example 1 to obtain an oral preparation.

Comparative Example 3 A film-like adherent was prepared in the same manner as in Example 3. On the other hand, separately from this, a solution in which 2 parts of azulene was dissolved in a small amount of methanol was prepared, and this was treated with ethylene in the same manner as in Example 3.
It was added to a mixed solution of vinyl acetate copolymer and toluene and stirred uniformly to form a film-like support by a conventional method. After that, both were thermocompression bonded in the same manner as in Example 3 to obtain an oral preparation.

Characteristic tests of the oral preparations obtained in the above Examples and Comparative Examples were conducted. The results are shown in the table below.

As is clear from the above table, the oral preparation containing the topical drug-containing water-absorbing polymer substance has a longer adhesion time and a longer drug release time than those containing no oral drug. Therefore, it has been shown to be effective even in a practical application test for healthy people. Furthermore, it can be seen that it is particularly effective for patients with castration who often have salivation and patients with postoperative bleeding.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yuji Ogishi 3-1, Asahi-cho, Takatsuki-shi, Osaka Sunstar Co., Ltd. (72) Inventor Tetsuo Horiuchi 1-2-1, Shimohozumi, Ibaraki-shi, Osaka Nitto Inside the Electric Industry Co., Ltd. (72) Inventor Yuichi Inoue 1-2 1-2 Shimohozumi, Ibaraki City, Osaka Prefecture Nitto Electric Industry Co., Ltd.

Claims (4)

[Claims] 1. An oral bandage comprising an integrated body of a film-like adherent and a flexible film-like support, wherein the film-like adherent is at least one of a polycarboxylic acid and a polycarboxylic anhydride and a vinyl acetate polymer. An oral preparation comprising a flexible film-shaped material in which and are in a compatible state, and a topical drug-containing water-absorbing polymer substance dispersedly contained in the flexible film-shaped support. 2. The oral preparation according to claim 1, wherein the film-shaped adherent contains a salt having a neutralizing effect on polycarboxylic acid or polycarboxylic anhydride. 3. The oral preparation according to claim 2, wherein the salt is at least one of a salt and a base. 4. The oral preparation according to claim 1 or 2, wherein the flexible film support is a plastic film.