JPH02209806A - Oral adhesive bandage - Google Patents

Abstract

PURPOSE:To provide the subject bandage having a sufficient adhesivity to oral membrana muscosa and excellent water resistance comprising a film made of a muscosa-adhesive base material containing a hydrophilic polymer and chitosan in a non-dissolving state. CONSTITUTION:An orally adhesive bandage comprises a film made of a membrana muscosa-adhesive base material containing a hydrophilic polymer having acidic groups such as carboxyl groups, hydroxyl groups or sulfonic groups, soluble in water and soluble in a solvent, (etc., a highly polar solvent such as an alcohol or acetone) capable of being mixed with water and chitosan or a derivative thereof, preferably having a shape of 100 meshes-passing particles or short fibers having diameters of <=10mum and lengths of <=1mm, or a laminate prepared by laminating a membrana muscosa-non-adhesive backing material to the film. The hydrophilic polymer and the chitosan (derivative) are used preferably in a weight ratio (chitosan/polymer) of 5/95-70/30.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention provides 9
Alternatively, the present invention relates to an intraoral bandage for absorbing a drug through the oral mucosa.

(Conventional technology) For the purpose of protecting damaged and diseased areas in the oral cavity.

Alternatively, an intraoral patch preparation (bandage) is prepared for the purpose of absorbing a prescribed medicinal ingredient into the body through the oral mucosa.0 An intraoral patch preparation (bandage) should be applied to the wet oral mucosa. It must be possible to remove the adhesive and not be easily peeled off due to saliva secretion, eating or drinking, etc. As a bandage for intraoral application, for example,
No. 8-7605 discloses a bandage for intraoral application having a composition containing hydroxypropyl cellulose and an acrylic acid (co)polymer or a salt thereof. Japanese Patent Publication No. 5
No. 9-186913 discloses gelatin or agar.

Oral bandages are disclosed whose compositions include gluten, carboxyvinyl polymer, and vinyl acetate or gums. In Japanese Patent Application Laid-Open No. 60-215622,
A bandage for intraoral application having a composition comprising polyvinyl bilonidone, polyvinyl alcohol, polyethylene glycol, alginic acid or a salt thereof, maleic anhydride-methyl vinyl ether copolymer, and acrylic acid (co)polymer is disclosed. JP-A-60-142927 discloses a bandage for intraoral application containing chitosan or a chitosan derivative. Japanese Unexamined Patent Publication No. 61-24
Publication No. 9473 discloses a bandage for intraoral application having a composition containing a polycarboxylic acid, a polycarboxylic anhydride, and a vinyl acetate copolymer.

The bandages disclosed in each of the above-mentioned publications all have a base containing a hydrophilic polymer as a main component. When such a hydrophilic polymer is exposed to a small amount of water such as saliva in the oral cavity, it becomes sticky and adheres to the mucous membrane of the oral cavity. However, a hydrophilic polymer alone swells and disintegrates due to large amounts of water from saliva or eating and drinking. In order to compensate for this lack of water resistance, in each of the above-mentioned publications, a water-insoluble or poorly water-soluble polymer is contained in the base in addition to the hydrophilic polymer. In this way, water insoluble (poorly soluble)
Although the presence of the polyester polymer improves water resistance, it has the disadvantage of reducing the adhesion of the base to mucous membranes. As described above, at present, a bandage for intraoral application that has good adhesion to the oral mucosa and sufficient external water resistance has not been obtained.

(Problems to be Solved by the Invention) The present invention solves the above-mentioned conventional problems, and aims to provide a material that has sufficient adhesion to the oral mucosa and has excellent water resistance. An object of the present invention is to provide a bandage for intraoral application.

(Means for Solving the Problems) The bandage for intraoral patching of the present invention is a film made of a base material that sticks to mucous membranes, or a laminate in which the film is laminated on a backing member that does not stick to mucous membranes. A bandage for internal application, wherein the base for application to mucous membranes contains a hydrophilic polymer and undissolved chitosan or a derivative thereof, and has the flexibility necessary for application inside the oral cavity. The above objective is achieved.

The hydrophilic polymer contained in the mucosal adhesive base of the bandage for intraoral application of the present invention includes carboxyl groups, hydroxyl groups,
It is a polymer with acidic groups such as sulfonic acid residues.

These polymers are water-soluble and water-miscible solvents, e.g.

It is soluble in at least one of the following: highly polar solvents such as alcohols, acetone, and acetonitrile. Examples of such polymers include poly(meth)acrylic acid, poly(meth)acrylic anhydride, maleic anhydride (co)polymer, and the like. These polymers absorb small amounts of water and become highly adhesive, as described in the prior art section.

The chitosan used in the present invention is chitin (β-1,4-
It is a deacetylated product of poly-N-acetylglucosamine), mainly consisting of a β-1,4-polyglucosamine structure, and has a free amino group.

In the present invention, chitosan and its derivatives (including chitin, chitosan salts and chitosan analogues) are used (hereinafter referred to as "chitosan and its derivatives").
(denoted as “chitosan”). When such chitosan is present in an undissolved state in the base for application to mucous membranes, it is preferably in the form of particles or short fibers, for example.

This chitosan, which is preferably formed into particles that pass through 100 meshes, and the hydrophilic polymer are mixed at a weight ratio of 5/95 to 70/30. If the hydrophilic polymer is in excess and the chitosan is in excess, the resulting bandage will have poor water resistance.

On the other hand, if the hydrophilic polymer is too small and the chitosan is too large, the adhesion to the oral mucosa will be poor.

The mucosal adhesive base may further contain a water-soluble compound having an acidic group. Such a compound is 1
It is a water-soluble compound that usually has 9 carboxyl groups in its molecules, examples of which include dicarboxylic acids such as oxalic acid and fumaric acid; acidic polyhydric acids such as pectic acid, alginic acid, and carboxymethyl cellulose. or salts thereof; and salts of (meth)acrylic acid (co)polymers.

In addition to the above, drugs and various additives may be contained in the mucosal adhesive base, if necessary. Examples of additives include drug absorption enhancers, antibacterial agents, and emollients.

These include surfactants, crosslinking agents, neutralizing/buffering agents, organic or inorganic fillers, fragrances, 9 colorants, 9 flavorings, etc.

The non-adhesive lining member used in the intraoral bandage of the present invention is a film made of a water-insoluble or poorly water-soluble polymer. As such water-insoluble or poorly water-soluble polymers, (meth)acrylic acid ester copolymers and the like are preferably used.

The bandage for intraoral application of the present invention is prepared in the following manner. When the bandage consists of a single layer of film with a mucosal adhesive base9, for example, the above-mentioned hydrophilic polymer and, if necessary, drugs and additives are uniformly dissolved or dispersed in an organic solvent such as ethanol, and chitosan is added to this. Add and mix to uniformly disperse the chitosan. A bandage for intraoral application is obtained by casting this mixture onto a release sheet and drying it. The thickness of the single-layer bandage for intraoral application is 10 to 10 seconds, preferably 2
It is a 0-500μ candle. When the bandage is composed of two layers: a base film that sticks to mucous membranes and a backing member that does not stick to mucous membranes, 1. For example, a mixture containing the hydrophilic polymer and chitosan is placed on the water-insoluble or poorly water-soluble film. Obtained by casting and drying. Alternatively, it can be obtained by laminating a single-layer mucous membrane adhesive base film formed on the above-mentioned release sheet and the above-mentioned water-insoluble or poorly water-soluble film. The thickness of the backing member of a bandage formed of such two layers is 5 to 500 μm.
m, preferably 10-100 μ steel, and.

The thickness of the mucous membrane adhesive base layer is 10 to 10 seconds, preferably 20 to 500 μm.

(Function) When the intraoral patch bandage of the present invention, which is a single-layer film made of a mucosal adhesive base, is applied to the oral mucosa, the hydrophilic polymer absorbs moisture in the oral cavity and becomes sticky, causing the mucosa to become sticky. Adheres to surfaces.

If this bandage is left attached to the oral mucosa, 1
Hydrophilic polymers become excessively water-absorbed due to water from saliva in the oral cavity and from eating and drinking. In such a state, the chitosan contained in the base material interacts with the acidic groups of the hydrophilic polymer, and as a result.

The hydrophilic polymer becomes insolubilized. Although this interaction is not clear, it is due to ionic bonds or hydrogen bonds between the amino groups of chitosan and the acidic groups 9 of the hydrophilic polymer, such as carboxyl groups. This is thought to be due to the bond between chitosan and the hydrophilic polymer. This effect is enhanced when a water-soluble compound having an acidic group is further present in the base.

The bandage of the present invention having a backing member that does not stick to mucous membranes reduces the amount of moisture absorbed per unit time by the base for sticking to mucous membranes when the bandage is applied, and also reduces the amount of moisture absorbed by the base for sticking to mucous membranes due to physical stimulation. Since the collapse of the layer is suppressed, it has better water resistance and durability, and can be applied to the surface of the oral mucosa for a long period of time.

In this way, a bandage is obtained that has good adhesion to the surface of the oral mucosa, has excellent water resistance, and can be applied to the oral mucosa for a long period of time. Since this bandage is in the form of a flexible sheet, it does not cause any discomfort when applied to the surface of the oral mucosa. The mucosal adhesive base that has absorbed moisture forms an elastic body, and therefore has a high effect of covering and protecting damaged and diseased areas within the oral cavity. Antibacterial and antiviral effects and wound healing promoting effects are also expected from the chitosan contained in the mucosal adhesive base.

(Example) The invention will be explained below with reference to examples.

(A) Preparation of bandage for intraoral application: Eudrag
20 parts of itRS (manufactured by Roha+ Pharma; methacrylic acid ester polymer) and 10 parts by weight of sorbitan monolaurate as a plasticizer were uniformly dissolved in ethanol. This solution was cast on a polyethylene terephthalate (PET) film whose surface had been treated with silicone and dried to obtain a film-like backing member having a thickness of 60 III m. Next, polyacrylic acid (¥1 water-based polymer)
5 parts by weight were uniformly dissolved in 95 parts by weight of ethanol.

In this solution, short fiber chitosan acetate (fiber diameter 1μ■;
2.5 parts by weight (fiber length: 500 μm) were mixed to prepare a uniform dispersion.

This solution was cast and dried on the film-like backing member, and the PBT was removed to obtain a bandage for intraoral application having a total thickness of 100 μm.

(B) Performance evaluation of bandage: Punch out the bandage obtained in (A) to a diameter of 10 mm, and add 10 d of water at 37°C.
It was crushed and left for 24 hours. When the properties of the adhesive were observed after being left as they were, it was confirmed that although the adhesive base for mucous membranes was cloudy, it remained integrated with the backing member.

Next, punch out a new bandage to a diameter of 10mm.

It was applied to wet regenerated pork skin and left for 10 minutes, and then the state of adhesion was observed. The bandage adhered well to the regenerated pork skin and showed resistance to peeling off.

Furthermore, the bandage after being left for 10 minutes was immersed together with the pork skin in water and left for 5 hours. As a result of observing the adhesion state after 5 hours, it was found that the bandage was sufficiently adhered to the pigskin and exhibited the same resistance when peeled off as before being immersed in water.

On charcoal (A) Preparation of bandage for intraoral application: Same as Example 1 except that chitosan acetate was not used.

(B) Performance evaluation of bandage: Using the bandage obtained in section (8) of this comparative example, evaluation was carried out in the same manner as in section (B) of Example 1. In the 24-hour underwater immersion test of the bandage,
The mucosal adhesive base completely dissolves in water.

It was observed that only the backing member remained.

In a test in which a bandage applied to pig skin was immersed,
A considerable portion of the mucosal adhesive base is eluted into water.
The bandage could be easily peeled off from the pork skin.

In this way, Example 1 and Comparative Example 1 are compared.

Although the initial adhesion strength of both bandages is the same.

It can be seen that the bandage of Example 1 containing chitosan acetate has much better water resistance than the bandage of Comparative Example 1 which does not contain chitosan acetate.

1 vessel ± 1 Six types of non+ndage were prepared by changing the blending ratio of short fibrous chitosan acetate and polyacrylic acid in Example 1 as shown in the table below. Each of the obtained bandages was punched out to a diameter of 10 mm and applied to regenerated pig skin in the same manner as in Example 1, and the state of adhesion was evaluated after 10 minutes. Furthermore, in the same manner as in Example 1, the state of adhesion to pig skin after immersion in water for 5 hours was evaluated. The results are shown in the table below.

(Left below) From the table, the blending ratio of chitosan acetate: polyacrylic acid is:
Considering stickiness and water resistance, 5/95 to 70/3
It can be seen that 0 (weight ratio) is appropriate.

Practical base (A) Preparation of bumps for intraoral application Two sets: 20 parts by weight of polyacrylic acid was used as the aqueous polymer.

This and 10 parts by weight of poly(N-vinylpyrrolidone) were dissolved in 160 parts by weight of ethanol, and 10 parts by weight of short fiber chitosan acetate similar to that used in Example 1 was added to this and uniformly dispersed. . This was cast onto the same backing member as in Example 1, and the total thickness was 10 mm in the same manner as in Example 1.
A 0 μm bandage was obtained.

(B) Bandage performance evaluation 2 Using the bandage obtained in Example (A), the adhesion to pig skin was evaluated in the same manner as in Example 1 (B). the result.

Adherence after 10 minutes and after 5 hours was good, and water resistance was also sufficient.

Next, the bandage obtained in Example 9 (A) was newly punched out to a diameter of 20 mm and applied to the oral mucosa of five panelists, and the time until peeling was measured. As a result, the average peeling time was 11.2 hours.

Preparation of a bandage for intraoral application (A): 20 parts by weight of polyacrylic acid was used as a hydrophilic polymer, and 0.1 part by weight of prednisolone was dissolved in 80 parts by weight of ethanol. In this solution, 5 parts by weight of oxalic acid and 20 parts by weight of 200 mesh chitosan were uniformly dispersed. This dispersion was cast on a POET film whose surface had been treated with silicone and dried to obtain a mucous membrane adhesive base film with a thickness of 80 μm. Separately, 60 parts by weight of polyvinyl acetate and 30 parts by weight of triethyl citrate as a plasticizer were uniformly dissolved in 110 parts by weight of ethanol.
A film-like backing member having a thickness of 601 mm was prepared by casting and drying on a T film. The above-mentioned mucosal adhesive base film and the backing member were thermocompression bonded to obtain an intraoral adhesive bandage.

(B) Bandage performance evaluation 2 Using the bandage obtained in Example (A), the adhesion to pig skin was evaluated in the same manner as in Example 1 (B). the result.

Adherence was good after 10 minutes and after 5 hours of immersion.

Water resistance was also sufficient.

(8) Preparation of bandage for intraoral application: 40 parts by weight of polyacrylic acid was used as a hydrophilic polymer, and this was dissolved in 120 parts by weight of ethanol. In this solution, 20 parts by weight of sodium alginate and 20 parts by weight of short fiber O-acetylchitosan acetate were uniformly dispersed. This dispersion was cast on a PET film whose surface had been treated with silicone and dried to obtain a 40 μm thick base film for sticking to mucous membranes.

Separately, 60 parts by weight of polyvinyl acetate and 30 parts by weight of triethyl citrate were dissolved in ethanol. This solution was cast on a PET film whose surface had been treated with silicone and dried to obtain a film-like backing member having a thickness of 100 μm.

The above-mentioned mucosal adhesive base film and the backing member were thermocompression bonded to obtain an intraoral adhesive bandage.

(B) Performance Evaluation of Bandage Two Comparative Examples Using the bandage obtained in Section (A), the adhesion to pig skin was evaluated in the same manner as in Section (B) of Example 1. the result.

Adherence was good after 10 minutes and after 5 hours of immersion.

Water resistance was also sufficient.

Northern comparison 1 (A) Preparation of bandage for intraoral application: Same as Example 4 (A) except that oxalic acid and chitosan were not used.

(B) Performance Evaluation of Bandage Two Comparative Examples Using the bandage obtained in Section (A), the adhesion to pig skin was evaluated in the same manner as in Section (B) of Example 1. the result.

Adherence was good after 10 minutes, but in a test in which the whole pig skin was immersed in water, the mucosal adhesive base dissolved in water after 5 hours, and only the lining material remained in the water. was confirmed.

From Example 4.5 and Comparative Example 2, the bandages containing chitosan and oxalic acid or sodium alginate have the same initial adhesive strength to the mucosal surface, but the former has much better water resistance. I know it's excellent.

(Effects of the Invention) According to the present invention, there is provided a bandage for intraoral application that exhibits excellent adhesion to two oral mucous membranes and has excellent water resistance. This bandage is in the form of a flexible sheet, so it does not cause any discomfort when applied, and
It has the effect of sufficiently protecting the mucous membrane area to which it is applied. Such a bandage can be applied to the oral mucosal surface for a long period of time, and can sufficiently protect injured or diseased areas within the oral cavity, for example. Antibacterial and antiviral effects and wound healing promoting effects can also be obtained from chitosan.

that's all

Claims (1)

[Scope of Claims] 1. An intraoral patch bandage comprising a film made of a mucosal adhesive base or a laminate in which the film is laminated on a non-mucosal adhesive backing member, the bandage comprising: 1. A bandage for intraoral application, the adhesive base of which contains a hydrophilic polymer and undissolved chitosan or a derivative thereof, and has the flexibility necessary for application within the oral cavity. 2. The bandage according to claim 1, wherein the hydrophilic polymer has an acidic group. 3. The bandage according to claim 1, wherein the hydrophilic polymer is soluble in water and soluble in at least one solvent miscible with water. 4. The hydrophilic polymer is (meth)acrylic acid (co)
The bandage according to claim 1, which contains at least one of a polymer or a (meth)acrylic anhydride (co)polymer. 5. The bandage according to claim 1, wherein the mucosal adhesive base further contains a water-soluble compound having an acidic group. 6. Claim 1, wherein the weight ratio of the hydrophilic polymer and chitosan or its derivative (chitosan or its derivative/hydrophilic polymer) of the mucous membrane adhesive base is 5/95 to 70/30. Bandage as described. 7. If the shape of the chitosan or its derivative for the mucous membrane adhesive base is granular, it is a particle that passes through 100 mesh, and if it is short fiber, the fiber diameter is 10 μm or less,
The bandage according to claim 1, wherein the fiber length is 1 mm or less. 8. The bandage according to claim 1, wherein the backing member that does not stick to mucous membranes is made of a water-insoluble or slightly water-soluble base.