JP2716195B2 - Oral bandage - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a bandage for oral application to protect a damaged or diseased part in the oral cavity or to absorb a drug through the oral mucosa. .

(Prior art) In recent years, for the purpose of protecting a diseased part of the oral cavity such as gingivitis or aphtha, or to absorb a predetermined medicinal ingredient into the body through the oral mucosa, a preparation for oral application (bandage) ) Has been prepared. The bandage for oral application is required to be able to be applied to wet oral mucosa and not to be easily peeled off due to secretion of saliva or eating and drinking.

The following technology has been proposed as such a bandage for intraoral application.

JP-B-61-25687: a two-layer structure comprising a water-soluble layer composed of a water-soluble polymer and a plasticizer, and a water-soluble layer composed of a crosslinked product of a water-soluble polymer and a plasticizer.

JP-A-58-90507: Production method in which a water-soluble polymer solution containing a poorly water-soluble agent and a plasticizer is applied to one surface of a film composed of a water-soluble polymer and a plasticizer.

JP-A-58-213709: A composition obtained by laminating a composition comprising one or more water-soluble or water-swellable polymer substances on a flexible support.

JP-A-59-196814: A composition comprising gelatin or agar, gluten, a carboxyvinyl polymer and a vinyl acetate resin or gums spread and coated on a support.

JP-A-61-249472: An integrated product of a mucosa-adhering base comprising a polycarboxylic acid, a polycarboxylic anhydride and a vinyl acetate polymer and a flexible film-like support.

JP-A-62-22713: a layer comprising a water-insoluble non-sticking layer and an adhesive layer comprising polyacrylic acid and polyethylene glycol.

Including the inventions disclosed in each of the above publications, generally, the mucosa-adhering base of the bandage for intraoral application, a hydrophilic polymer is used as an oral mucosa-adhering component, and in order to be able to withstand prolonged application In addition, a water-insoluble polymer such as a vinyl acetate resin is mixed as a water-resistance imparting component, or laminated on a water-insoluble support.

(Problems to be Solved by the Invention) As described above, the bases disclosed in the above publications have been devised so that they can be stuck to the oral mucosa for a long time. Under severe conditions such as secretion, physical irritation accompanying eating and drinking, conversation, etc.
In order to be able to adhere to the oral mucosa for a long time under such conditions, the adhesiveness, water resistance and flexibility of the base are indispensable.

However, since the above-mentioned base uses a vinyl acetate resin as a water resistance imparting component, it has poor flexibility and cannot withstand severe movement of the oral mucosa. JP-B-57-6403 and JP-A-59-196814 propose a technique using a plasticizer such as a polyhydric alcohol in order to impart flexibility. Therefore, it has poor water resistance and has a disadvantage that it collapses in a short time.

In addition, there is also a problem that a support laminated on a water-insoluble support is apt to peel off when the base contains water.

An object of the present invention is to solve the above-mentioned conventional drawbacks, and an object of the present invention is to provide a bandage for oral application that has sufficient adhesion to the oral mucosa, and is excellent in water resistance and flexibility. Is to provide.

(Means for Solving the Problems) The present inventors have prepared a mucosa-adhesive base using a composition comprising a vinyl acetate resin and a certain kind of hydrophilic polymer and a plasticizer, whereby the flexibility is improved. It has been found that a base having good adhesive properties can be obtained on a wet mucosal surface, and furthermore, in this case, it has been found that the type of the plasticizer greatly varies the water resistance and disintegration of the bandage. As a result of intensive investigations in pursuit of this cause, the use of a water-insoluble substance as a plasticizer does not reduce the water resistance and also prevents the base from collapsing. And reached the present invention.

The adhesiveness and water resistance of the film-like mucosa-adhering base of the present invention are sufficiently satisfactory alone, but the film-like support comprising the above-mentioned vinyl acetate resin and a water-insoluble plasticizer is also used. Integrate, at the time of sticking, by imparting water resistance by preventing the support from peeling even if it contains water,
The present invention has been completed based on the finding that the sticking time can be improved.

That is, the bandage for oral application of the present invention is a bandage for oral application consisting of a laminate of a film-like mucosa-adherable base and a film-like support, wherein the mucosa-adhesive base is vinyl acetate. The resin and the hydrophilic polymer, and contains a water-insoluble plasticizer having a plasticizing effect on the vinyl acetate resin, the support contains a vinyl acetate resin and a water-insoluble plasticizer, thereby achieving the above object. You. In the present invention, the term “film” includes a relatively thin sheet to a relatively thick sheet.

The hydrophilic polymer contained in the mucosa-adhering base of the bandage for intraoral application of the present invention may be a polymer that dissolves or swells in water, and such a hydrophilic polymer includes
For example, the following are mentioned.

Water-soluble cellulose ethers: methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and the like.

Polysaccharides: gum arabic, gum tragacanth, pectin,
Alginic acid and its sodium salt, agar, dextrin, dextran, amylose and the like.

Synthetic polymer: polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, etc.

These hydrophilic polymers absorb a small amount of water and have a strong adhesive force.

Examples of the vinyl acetate resin used in the present invention include a vinyl acetate homopolymer and a copolymer of vinyl acetate and a vinyl monomer such as ethylene or an acrylate.

Examples of the water-insoluble plasticizer having a plasticizing effect on the vinyl acetate resin used in the present invention include the following compounds.

Essential oils: orange oil, cinnamon oil, clove oil, etc.

Surfactants: sorbitan monolaurate, polyoxyethylene hydrogenated castor oil and the like.

The mixing ratio of the plasticizer to the vinyl acetate resin can be in any range that can plasticize the vinyl acetate resin, and can be appropriately changed depending on the type of the plasticizer used.

The mixture ratio of the mixture of the vinyl acetate resin and the plasticizer and the hydrophilic polymer is preferably 2/8 to 7/3 by weight. If the amount of the hydrophilic polymer is more than the above range, the resulting bandage will have poor water resistance, and if the amount of the hydrophilic polymer is too small, the adhesiveness to the oral mucosa will be poor.

In the mucosa-adhering base, if necessary, various medicinal ingredients, absorption promoters for medicinal ingredients, antibacterial agents, softeners, surfactants, crosslinking agents, neutralizing / buffering agents, organic or inorganic bulking agents , Fragrances, colorings, flavors / flavors and the like can be added.

The support used in the bandage for intraoral application of the present invention is a water-insoluble or hardly water-soluble support, and is a film-like one formed of a composition containing a vinyl acetate resin and a water-insoluble plasticizer. The vinyl acetate resin and the water-insoluble plasticizer are selected from those described above. The same type of vinyl acetate resin is preferably used for the base and the support.

The bandage for application to the oral cavity of the present invention may be prepared by any method, for example, the following method.

A vinyl acetate resin and a water-insoluble plasticizer are uniformly dissolved in an organic solvent such as ethanol, and this mixture is cast on a release sheet and dried to form a film to obtain a flexible support. On the other hand, a vinyl acetate resin, a water-insoluble plasticizer, and a hydrophilic polymer are uniformly dissolved in an organic solvent such as ethanol, and if necessary, an additive such as a medicinal ingredient is added thereto. It is integrated by casting and drying. Alternatively, instead of dissolving the same mixture in an organic solvent, heating and kneading are performed to obtain a paste-like mucoadhesive base composition, which is extruded or pressed to form a film. It is obtained by laminating on top by extrusion or pressing. The thickness of the support of such a two-layered bandage is preferably 5 to 500 μm, more preferably 10 to 100 μm.
m, and the thickness of the mucosa-adhering base is preferably from 10 to 5,000 μm, more preferably from 20 to 500 μm.

(Function) When a hydrophilic polymer inherently absorbs a small amount of water, it has a strong adhesive force. In the present invention, the adhesive property inherent in the hydrophilic polymer can be maintained by the presence of the hydrophilic polymer in the base.

Further, the presence of the vinyl acetate resin, which is a water-insoluble polymer, in the base can improve the water resistance of the base. Furthermore, since a water-insoluble plasticizer is blended, the plasticizer does not elute even when applied on a wet surface, preventing the base from collapsing and allowing long-time application, and at the same time, vinyl acetate. Since it has a plasticizing effect on the resin, it is possible to impart flexibility to the base.

The bandage of the present invention, which is constituted by laminating a support on a mucosa-adhesive base, reduces the amount of water absorbed per unit time of the mucosa-adhesive base and physically The relaxation of the irritation suppresses the disintegration of the mucosa-adhering base layer, makes it more water-resistant and more durable, and makes it possible to adhere to the oral mucosa surface for a long time. Moreover,
Since the composition of the support is almost the same as the components of the mucosa-adhesive base, the support and the base are integrated, and the base and the support are firmly adhered to each other. Therefore, even if the base contains water, the support does not peel off.

(Examples) Hereinafter, the present invention will be described with reference to examples.

Comparative Example 1 70 parts by weight of vinyl acetate resin, 30 parts by weight of orange oil, and 100 parts by weight of sodium alginate were mixed, heated, kneaded, made into a paste, and then pressed to give a flexible sheet-like mouth having a thickness of about 100 μm. A bandage for internal application was obtained.

Example 1 70 parts by weight of a vinyl acetate resin and 30 parts by weight of orange oil were dissolved in ethanol, and this mixture was cast on a release sheet and dried to obtain a flexible film-like support having a thickness of about 20 μm. The paste-like kneaded material obtained in Comparative Example 1 was placed on the support, and heated and pressed to obtain a flexible sheet-like oral adhesive bandage having a thickness of about 100 μm.

Comparative Example 2 The procedure of Comparative Example 1 was repeated, except that sorbitan monolaurate was used instead of the orange oil of Comparative Example 1, to obtain a flexible sheet-like oral bandage for oral application.

Example 2 The same as Example 1 except that a film-like support was prepared using sorbitan monolaurate instead of the orange oil of Example 1, and the paste-like kneaded product of Comparative Example 2 was used therefor. To obtain a flexible sheet-like bandage for intraoral application.

Comparative Example 3 The procedure of Comparative Example 1 was repeated, except that triethyl citrate was used instead of the orange oil of Comparative Example 1, to obtain a flexible sheet-like bandage for intraoral application.

Comparative Example 4 70 parts by weight of a vinyl acetate resin and 30 parts by weight of triethyl citrate were dissolved in ethanol, and this mixture was cast on a release sheet and dried to obtain a flexible film-like support having a thickness of about 20 μm. The paste-like kneaded material obtained in Comparative Example 3 was placed on this support, and heated and pressed to obtain a flexible sheet-like intraoral adhesive bandage having a thickness of about 100 μm.

Using the bandages for intraoral application obtained in Examples 1 and 2 and Comparative Examples 1 to 4, the following water resistance test and application test were performed.

(Water resistance test)

Japanese Pharmacopoeia The test was carried out using a tester used for the first method (rotating basket method) of the dissolution test method.

Put the bandage punched out to a diameter of 20 mm into the basket whose weight was measured in advance, measure the weight,
Spin at 100 rpm in 500 ml of water at 37 ° C. One hour after the start of the test, the basket was taken out, and the remaining state of the bandage was observed. After freeze-drying to evaporate the water, the weight was measured to determine the remaining rate.

(Pasteability test)

The bandage was punched out to a diameter of 20 mm, attached to wet regenerated pig skin, allowed to stand for 10 minutes, and then observed for adhesion. Further, the bandage left for 10 minutes was soaked in water together with the pig skin, left for 1 hour, and the state of adhesion after 1 hour was observed. Table 1 shows the results.

From the results shown in Table 1, the support was not peeled off from the base in all of the examples, and the water-insoluble plasticizer was used, so that the support was flexible and the adhesion was good and the water resistance was good. It was confirmed that by using the support prepared in the above, a bandage for intraoral application in which the support was not peeled off at the time of application could be obtained.

Example 3 Polyvinylpyrrolidone was blended in a ratio (weight ratio) shown in Table 2 with respect to a total of 100 parts by weight of 70 parts by weight of vinyl acetate resin and 30 parts by weight of orange oil to prepare an ethanol solution. 70 parts by weight of vinyl acetate resin and orange oil 30
Cast on a flexible support consisting of parts by weight, dry to about 100
Seven types of bandages for intraoral application with a thickness of μm were obtained.

Using this bandage, the above-mentioned water resistance test and sticking test were performed. Table 2 shows the results.

From the results in Table 2, it was found that the support did not peel in all of the examples, and the mixing ratio of the vinyl acetate resin and the plasticizer / hydrophilic polymer was 2/2 in consideration of the adhesive property and the water resistance. It turns out that 8-7 / 3 (weight ratio) is appropriate.

Example 4 70 parts by weight of vinyl acetate resin and sorbitan monolaurate
20 parts by weight, after adding 60 parts by weight of polyacrylic acid and 30 parts by weight of polyvinylpyrrolidone to make an ethanol solution,
This was cast on a flexible support consisting of 70 parts by weight of vinyl acetate resin and 20 parts by weight of orange oil, dried to about 150 μm
A m-thick bandage for intraoral application was obtained.

Example 5 70 parts by weight of vinyl acetate resin, 30 parts by weight of cinnamon oil, and 100 parts by weight of hydroxypropyl cellulose were mixed and heated.
After kneading and forming a paste, this was extruded on a flexible support consisting of 70 parts by weight of vinyl acetate resin and 20 parts by weight of sorbitan mon laurate by an extruder, and a flexible sheet having a thickness of about 150 μm was obtained. A bandage for sticking in the oral cavity was obtained.

Next, when the above-mentioned water resistance test and sticking property test were performed using the bandage for oral sticking obtained in Examples 4 and 5, the sticking property after 10 minutes and 1 hour was good,
The water resistance after one hour was also sufficiently satisfactory.

(Effects of the Invention) According to the present invention, there is provided a flexible bandage for oral application that exhibits excellent adhesiveness to the oral mucosa and is excellent in water resistance. Since this bandage has a flexible sheet shape, it does not give an uncomfortable feeling at the time of application, and has an effect of sufficiently protecting the applied portion of the mucous membrane. Such a bandage can be stuck to the surface of the oral mucosa for a long period of time, for example, can sufficiently protect damaged or diseased parts of the oral cavity, reduce external physical irritation, and heal Can be promoted,
It is also useful as a base for percutaneously absorbing a medicinal ingredient and exerting a systemic action / local action.

Claims (1)

(57) [Claims] 1. A bandage for oral application comprising a laminate of a film-like mucosa-adhering base and a film-like support, wherein the mucosa-adhering base is a vinyl acetate resin, a hydrophilic polymer, And a bandage for oral application which contains a water-insoluble plasticizer having a plasticizing effect on a vinyl acetate resin, and wherein the support contains the vinyl acetate resin and a water-insoluble plasticizer.