JPH072179B2 - Oral bandage and manufacturing method thereof - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention is intended to prevent the outflow of a drug that is applied to a moist mucous membrane in the oral cavity and is administered to the mucous membrane in the oral cavity and to protect the damaged portion of the mucous membrane in the oral cavity. The present invention relates to an oral bandage to be performed and a manufacturing method thereof.

[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 or eating and drinking, and it is difficult to exert a sufficient drug effect. is there.

In addition, it is rarely done to cover and protect the damaged part in the oral cavity because there is no effective oral bandage, but saliva is constantly secreted in the oral cavity as described above and food and drink enter. Therefore, there is a major obstacle to the realization of the coating protection.

Recently, various proposals have been made in order to overcome these obstacles and effectively administer a drug to oral diseases. Among them, as a concept relatively close to the oral cavity dressing of the present invention, there is an oral mucosa-adhesive preparation containing a water-soluble polymer substance as an adhesive component. The water-soluble polymer substance varies in degree depending on its type, but when it absorbs a small amount of water, it becomes a viscous aqueous solution or gel and exhibits adhesiveness. Utilizing this property, paste (Japanese Patent Publication No. 56-27491), sponge (Japanese Patent Publication 56-2)
5211), tablet-shaped (JP-B-58-7605), sheet-shaped (JP-B-44-16676, JP-A-59-1)
A variety of preparations having mucoadhesive properties in the oral cavity have been devised.

[Problems to be solved by the invention]

However, each of the above-mentioned preparations only adheres to the mucous membrane of the oral cavity and administers a visceral drug, and it is sufficient if it has sufficient adhesive force to administer the visceral drug and is sufficient for administration of the drug. Since it is sufficient to adhere to the mucous membrane only for a certain period of time, it does not have the strong adhesive force and long-term adhesive force required for the oral bandage. That is, the oral dressing is applied on the diseased part or damaged part in the oral cavity, and is intended to prevent the washout of the drug administered thereto or to protect the coating on those parts, such as bleeding from the administered drug or the damaged part. Therefore, it is required to have an adhesive force capable of strongly adhering to the oral mucosa, which is in a state where it is difficult to adhere, and an adhesive sustaining force to adhere for a long time. The oral mucosa-adhesive formulation is, by its nature, not as adhesive and persistent as required for an oral dressing as described above.
Therefore, even if the base of the preparation is transferred to an oral dressing, the above-mentioned properties required for the oral dressing cannot be fully exhibited. Needless to say, adhesive tapes such as bandages used for the outer skin do not have adhesiveness to moist surfaces such as the mucous membrane of the oral cavity, and therefore cannot be diverted to oral bandages.

The oral dressing is applied to the diseased part of the oral cavity, etc., and since it exerts the action of preventing the washout of the administered drug and the protective action of the coating, it is required to have strong adhesive force and long-term adhesion as described above. In addition, it is flexible enough to be applied to any part of the oral mucosa with a complicated shape and has storage stability that does not deteriorate even under severe conditions such as storage and transportation. Is required. However, the reality is that there is no such thing.

The present invention has been made in view of the above circumstances, and provides a strong adhesive force, a long-lasting adhesive force, flexibility that can be applied to any part of the oral mucosa, and severe conditions. Another object of the present invention is to provide an oral bandage having storage stability that does not deteriorate and a method for producing the same.

[Means for solving problems]

In order to achieve the above object, the present invention is an oral bandage consisting of a film-like adherent alone or an integrated product of a film-like adherent and a flexible film-like support, wherein the film-like adherent is a poly At least one of a carboxylic acid and a polycarboxylic anhydride and a vinyl acetate polymer are in a compatible state, and an oral dressing composed of a flexible film containing a surfactant. As a first gist, a step of dissolving at least one of a polycarboxylic acid and a polycarboxylic acid anhydride and a vinyl acetate polymer in a common solvent and adding a surfactant, and a step of forming the above solution into a film shape are included. A second aspect of the present invention is a manufacturing method of the provided oral bandage.

Water-soluble polymer substances such as polycarboxylic acid and polycarboxylic acid anhydride have shape-retaining property by themselves, and exhibit strong adhesiveness in the state of absorbing a small amount of water, but immediately in the state of excessive water absorption. Then, the viscosity is lowered and the particles are disintegrated to become substantially dissolved in water to lose the adhesiveness.

The present inventors make use 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 cavity dressing, and 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. It has been found that when the above-mentioned compatibilized product further contains a surfactant, the strong adhesive force does not decrease even under severe conditions and excellent storage stability is exhibited. The invention was reached.

Here, the compatible state means that at least one of polycarboxylic acid and polycarboxylic acid anhydride (hereinafter collectively referred to as “polycarboxylic acids”) and vinyl acetate polymer are phase-separated to form an independent small region. It means a state in which they are dissolved uniformly without any

As described above, the present inventors have found that 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, for example, in water. We have found that even if it is immersed for a long time, it swells uniformly and does not disintegrate. Utilizing this property, we investigate the compatibility state of polycarboxylic acids and vinyl acetate polymers. You can That is, in the present invention, the compatibility state of the polycarboxylic acid and the vinyl acetate polymer is to be examined from the elution amount of the polycarboxylic acid, and the compatibility state in the present invention is specifically the following dissolution rate measurement. Dissolution rate obtained by the method is 50% by weight
(Hereinafter, abbreviated as "%") It means a mixed state that is the following.

<Elution rate measurement method> A film (film-like adhered material) composed of polycarboxylic acids, a vinyl acetate polymer and a surfactant is crushed at 0 ° C or lower and weighed. This is put 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 acid and the surfactant eluted in the purified water by this operation is determined by the weight reduction of the adhered body by immersion.
The dissolution rate is calculated by dividing this by the sum of the blending amounts of the polycarboxylic acids and the surfactant in the film.

The oral cavity dressing of the present invention not only seeks to enhance the adhesive strength when the polycarboxylic acid and the vinyl acetate polymer are made into a compatible state to form a film, and further contains a surfactant, so that the severe conditions The storage stability below has also been greatly improved, and performance will not deteriorate due to storage or transportation. This is the greatest feature of the present invention. That is, the film-like adherent composed of the compatible material of the polycarboxylic acid and the vinyl acetate polymer is stable under normal storage conditions. For example, the adhesive property even when stored at 40 ° C. and 75% RH for 6 months. Is not observed at all. However,
Under high temperature conditions of 50 ° C. or higher, the adhesive force rapidly decreases, and under 70 ° C., for example, the adhesive property is completely absent within a few days. And, the adhesive property once lost cannot be recovered. As described above, it is expected that the rapid decrease in the adhesion property under high temperature will be a practical obstacle in consideration of the inside of the vehicle in the summer, the inside of the warehouse, and the like.

Therefore, as a result of a series of studies to improve this point, the present inventors have found that the inclusion of a surfactant imparts stability at high temperature without deteriorating the adhesive property of the film-like adherent itself. The present invention has been achieved by finding out what can be done. Generally, the surfactant becomes present on the surface of the compound at a high concentration in a short period of time after compounding and impairs the adhesiveness and tackiness originally possessed by the compound surface. It has been considered that the incorporation into such a dense composition causes deterioration of the adhesion property. However, in the present invention, no deterioration of the adhesive property due to the surfactant is observed. It is considered that this is because the surfactant is not unevenly distributed on the surface and is dispersed in the film-like adherent to stabilize the compatibility state of the polycarboxylic acetic acid and the vinyl acetate polymer.

Thus, the oral dressing of the present invention comprises a substantially water-insoluble flexible film in which the polycarboxylic acetic acid and the vinyl acetate polymer are in a compatible state, and therefore, it lasts for a long time in a very thin state. In addition to exhibiting adhesion sustainability, since the above-mentioned compatible state is stabilized by the surfactant, the adhesion property does not deteriorate even under severe storage conditions such as exposure to high temperature.

The oral dressing of the present invention is, for example, a film-like adherent in which a polycarboxylic acid and a vinyl acetate polymer are dissolved in a common solvent, and a surfactant is further added and dissolved to rapidly cast and dry the same. It can be manufactured by This manufacturing method has an advantage that a very thin film-like body can be easily formed.

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, acrylic acid esters such as butyl acrylate and 2-ethylhexyl acrylate, methacrylic acid esters such as methyl methacrylate, and vinyl acetate. Examples thereof include a copolymer with a vinyl monomer and a copolymer such as carboxyvinyl polymer.
Further, specific examples of the methacrylic acid polymer include copolymers similar to those in the case of the acrylic acid polymer, in addition to the methacrylic homopolymer, 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.
Among these polycarboxylic acids, it is effective that the polycarboxylic acid contains 20% or more of —COOH groups and the polyanhydride carboxylic acid contains 16% or more of —CO—O—CO— groups. It is preferable above.

A typical example of the vinyl acetate polymer is a vinyl acetate homopolymer. In addition to this, a vinyl acetate homopolymer and a vinyl monomer copolymer such as an acrylic ester and a vinyl acetate homopolymer are partially saponified. Partially saponified compounds are also included. These can be used alone or in combination. The average molecular weight (viscosity average molecular weight) of these is preferably 60,000 or more. Average molecular weight is 6
If it is less than 0000, the water resistance of the above film-like adherent is lowered, and it is difficult to obtain the desired effect.

Typical examples of the above-mentioned surfactants are nonionic such as sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether and the like. Examples of the surface active agent include a single type and a mixed type. It is preferable that these have an HLB of 10 or more. HLB
If less than 10, it is difficult to obtain the effect of stabilizing the film-like adherent.

The common solvent for the polycarboxylic acids and the vinyl acetate polymer is a lower alcohol such as methanol or ethanol, and a mixture of the lower alcohol with an organic solvent such as soluble acetone or ethyl acetate, and the lower alcohol is 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. These solvents also dissolve the surfactant. 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. If it exceeds 30%, it becomes difficult to dissolve the polycarboxylic acids. Regarding 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 manufacturing an oral bandage as described above,
The mixing ratio of the polycarboxylic acid and the vinyl acetate polymer is
It is preferable to regulate the A value obtained by the following formula so that it falls 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. And the A value is
When it is less than 15, it becomes difficult to obtain sufficient adhesion, and when it exceeds 55, it becomes difficult to obtain sufficient adhesion durability. Therefore, it is preferable to control 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. Explaining the case where polyacrylic acid is used as the polycarboxylic acid as an example, the ratio of polyacrylic acid in the film-like adherent is 24 to
When it is in the range of 88%, the A value falls within the above range, and a preferable result can be obtained.

Further, the mixing ratio of the surfactant is preferably 0.5 to 10% with respect to the film-like adherent. 0.5
If it is less than 10%, it is difficult to obtain the stabilizing effect, and if it exceeds 10%, excessive surfactant may bloom (emboss on the surface) and the adhesiveness may be impaired.

Furthermore, when the above-mentioned polycarboxylic acids, vinyl acetate polymer and surfactant are dissolved in a common solvent, it is necessary to take care so that these three 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 to make sure that the concentration of the polymer substance does not exceed 40%.

The casting and drying film-like adherence of polycarboxylic acids, vinyl acetate polymer and surfactant is carried out by casting the above solution on a suitable film such as polyethylene laminated paper which has been subjected to a peeling treatment, and then drying it with a drier or a dryer. It can be done by rapid drying and filming by using a hot air bath such as a tower. The proper drying time or drying temperature depends on the composition of the common solvent, the solid content concentration in the solution,
Although it depends on the casting thickness and the like, under normal pressure, it is generally preferable to dry at a temperature of 60 to 120 ° C. for about 1 to 20 minutes.

Thus, a very thin film-like deposit is obtained. This film-like adherent can be used as it is in the oral cavity bandage of the present invention. In this case, the thickness of the film-like adherent can be adjusted by controlling the casting amount and the like,
It is preferable to regulate within the range of 10 to 100 μm. This is because if the thickness is less than 10 μm, it is difficult to develop sufficient adhesive properties, and if it exceeds 100 μm, a feeling of foreign matter in the mouth is likely to be given during use, and the flexibility of the film-like adherent tends to be impaired.

The intraoral bandage of the present invention can be constituted by only the above film-like adherent, but can also be constituted by combining this with a flexible film-like support.

Explaining the production method of this combination, this combination produces a film-like adherent as described above, and the film-like adherent is prepared by a conventional method such as thermocompression bonding or using an adhesive. It is also possible to produce a film-like adherent by casting the composition used for the production of a sheet-like adherent onto a flexible film-like support, and producing a film-like adherent and attaching it to a flexible film-like support. It can also be manufactured by performing the matching at the same time. In the latter case, there is an advantage that the thermocompression bonding and the bonding work become unnecessary and the manufacturing can be simplified.

It is preferable to use a water-impermeable material as the flexible film-shaped support. Typical examples are polyethylene, vinyl acetate resin, ethylene-vinyl acetate copolymer, polyvinyl chloride, polyurethane and other plastic films, aluminum foil, tin foil and other metal foils, cloth and paper and plastic films. Laminated film and the like. Of these, from the viewpoint of safety and usability, it is preferable to use a plastic film such as polyethylene, vinyl acetate resin, ethylene-vinyl acetate copolymer. Such a film-shaped support has a thickness of 10
It is preferable to use a film having a thickness of 30 to 150 μm in the range of 30 to 150 μm, because it is easy to handle and does not give a foreign body sensation during use. It is preferable to regulate it. That is, if the thickness is less than 30 μm, the handling and operability are deteriorated, and if the thickness exceeds 150 μm, a feeling of foreign matter tends to be given during use.

An oral bandage obtained by integrating a film-like adherent and a flexible film-like support as described above, by the action of the film-like adherent, strongly adheres to the oral mucosa,
Although it develops long-term adhesion sustainability, by integrating the flexible film-shaped support described above, the strength of the oral bandage increases and it becomes easier to use. Further, it is possible to obtain the effect of preventing foreign matter from being attached. And by using a water-impermeable flexible film,
It is possible to further obtain effects such as preventing moisture from entering from the back surface and extending the duration of adhesion.

It should be noted that it is free to add a coloring agent, a flavoring agent, a softening agent, a neutralizing agent, etc. to the film-like adherent or the film-like support of the oral dressing of the present invention within a range that does not impair the adhesiveness. . For example, in the case where both the adherent and the support are colorless, blending a coloring agent into one of the adherents and the support provides an advantage that the front and back of the bandage are clear and easy to use.

〔The invention's effect〕

The oral cavity dressing of the present invention is a compatibilized material of a polycarboxylic acid and a vinyl acetate polymer, which is substantially insoluble in water, and is constituted by using a thin flexible film containing a surfactant. The action of this film exerts a strong adhesive force to strongly adhere to the mucous membrane of the oral cavity and maintain that state for a long time. The above-mentioned oral bandage 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 attached to any part of the mucous membrane of the oral cavity. Moreover, the above-mentioned adhesive property does not deteriorate even under severe storage conditions such as high temperature due to the stabilizing effect of the surfactant contained in the film of the oral bandage.

An oral dressing having such an excellent effect is easily formed by dissolving polycarboxylic acids and a vinyl acetate polymer in a common solvent, further adding a surfactant and mixing the solution, and then forming this solution into a sheet shape. Can be manufactured.

Next, examples will be described together with comparative examples.

[Examples 1 to 6] Carboxyvinyl polymers were used as polycarboxylic acids, and 4.7 parts by weight of these (hereinafter abbreviated as "parts"), vinyl acetate resin (1500) 4.7 parts, trisodium citrate 0.3, and the following first The surfactants shown in the table were dissolved in a mixed solution of 80 parts of methanol and 10 parts of water to prepare a uniform solution. Next, this solution was cast on polyethylene laminated paper and dried by sensitizing for 5 minutes in a dryer at 100 ° C. to form a film-like adherent having a thickness of 30 μm. Then, the film-like adhered body was thermocompression-bonded to a film of vinyl acetate resin (1200) having a thickness of 3 μm at 120 ° C. to obtain a target oral bandage.

[Comparative Example 1] No surfactant was blended. Other than that, Example 1 above
The target oral bandage was obtained in the same manner as described above.

Regarding the example product and the comparative example product thus obtained,
Immediately after the oral bandage was obtained (initial stage) and at the time of storage at 70 ° C. for 3 days, an immersion test in water and a practical test were performed according to the following procedures.

<Immersion test in water> Cut a sample into a circle with a diameter of 10 mm and attach it on a water-swelling collagen film fixed on a Bakelite plate, at 37 ° C.
The sample was soaked in water and the time until the sample peeled off from the collagen film and spontaneously fell off was measured.

<Practical test> A sample was cut into a circle with a diameter of 10 mm, and the sample was attached to the palate of five healthy male panelists, and the time until peeling was measured and averaged. The pasting was done after lunch, and the students had the usual coffee and conversation.

Table 2 shows the results of the immersion test in water and the practical test.

From the above results, it is understood that all of the example products maintain the same strong adhesive force as in the initial stage even under the severe storage condition of 70 ° C. and have excellent storage stability.
On the other hand, the comparative example product loses its adhesive force completely when stored at 70 ° C, and is not suitable for carrying in a sunny car or as a fixture in a factory, warehouse, etc. where temperatures tend to be high. I understand.

[Example 7] The following raw materials were mixed and dissolved according to the following formulation, and the mixed solution was cast on an aluminum foil having a thickness of 15 µm and dried in a dryer at 80 ° C for 15 minutes to obtain a film having a thickness of 35 µm. The shaped body was made to obtain the desired oral bandage.

Carboxy vinyl polymer 6.0 parts Vinyl acetate resin 1500) 4.0 parts Polyoxyethylene (40) monostearate 0.5 parts Methanol 90.0 parts [Comparative Example 2] Polyoxyethylene (40) monostearate was blended. Otherwise, in the same manner as in Example 7 above, the target oral bandage was obtained.

Regarding the example product and the comparative example product thus obtained,
At the time of storage under the storage conditions shown in Table 3 below, an immersion test in water and a practical test were conducted in the same manner as described above. The results are shown in Table 3.

From the above results, it can be seen that the product of Example has a remarkable storage stability as compared with the product of Comparative Example.

[Example 8] The following raw materials were mixed and dissolved according to the following formulation, and the mixed solution was cast on a polyester film and dried in a dryer at 100 ° C for 10 minutes to form a film-like adherent having a thickness of 20 µm. Tsukutsuta. Then, apply this film-like adherent to a thickness of 25μ
m vinyl acetate resin (1200) film was thermocompression-bonded at 100 ° C. to obtain the target oral bandage.

Methyl vinyl ether maleic anhydride copolymer 4.0 parts Vinyl acetate resin (2000) 5.5 parts Diisopropanolamine 0.5 parts Polyoxyethylene (60) hydrogenated castor oil 0.2 parts Methanol 90.0 parts [Comparative Example 3] Polyoxyethylene (60) hydrogenated castor No oil blended. . Otherwise, in the same manner as in Example 8 above, the desired oral dressing was obtained.

With respect to the product of Example and the product of Comparative Example thus obtained, at the time of storage under the storage conditions shown in Table 4 below, an immersion test in water and a practical test were conducted in the same manner as described above. The results are shown in Table 4.

From the above results, it can be seen that the product of Example has a remarkable storage stability as compared with the product of Comparative Example.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Kenji Hasegawa, 3-1, Asahi-cho, Takatsuki-shi, Osaka Sunstar Co., Ltd. (72) Koichi Nakajima, 3-1-1, Asahi-cho, Takatsuki-shi, Osaka Sunstar Co., Ltd. Within

Claims (2)

[Claims] 1. An oral cavity dressing comprising a film-like adherent alone or an integrated product of a film-like adherent and a flexible film-like support, wherein the film-like adherent is a polycarboxylic acid and a polycarboxylic anhydride. An oral cavity dressing characterized in that at least one of the above and vinyl acetate polymer are in a compatible state, and the soft band-like body contains a surfactant. 2. A step of dissolving at least one of a polycarboxylic acid and a polycarboxylic acid anhydride and a vinyl acetate polymer in a common solvent and adding a surfactant, and a step of forming the solution into a film. A method for producing an oral bandage, which comprises: