JPH0458988B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a mucosal bandage that is applied to a moist mucous membrane, and more specifically, a bandage that fixes and coats a drug to be administered through a moist mucous membrane on a mucosal surface such as the oral cavity.
Another object of the present invention is to provide a mucosal bandage that covers and protects damage caused to mucosal surfaces such as the oral cavity.

Administration of drugs to moist mucous membranes such as the oral mucosa is useful not only when the mucous membrane is the diseased site but also when administering drugs that are difficult to absorb orally, such as hormones, because the mucosal area has relatively high drug absorption. Attempts are being made to use it for administration.

However, the biggest obstacle when administering drugs from such mucosal sites, especially oral mucosa, is that secretions such as saliva or the expansion and contraction of the mucosal site due to conversation, etc., prevent the placed drug from being absorbed until it is absorbed. The drug is washed away by the drug, and the pharmacological effect is not sufficient compared to the amount of drug.

In recent years, as preparations or analogues aimed at increasing drug retention and pharmacological effects,
Pastes containing sodium polyacrylate, sponges or tablets made of water-soluble polymer substances have been proposed in which the drug is contained in the base.

Although such pastes or preparations have considerably improved retention properties when compared to conventional ointment types, they are currently not satisfactory in the following respects.

That is, since the paste does not have sufficient physical strength, it has the disadvantage that it is easily removed due to expansion and contraction of mucous membranes or rubbing during conversation.

In addition, formulations have the disadvantage that it is difficult to adjust the type and amount of the drug to be administered depending on the type and symptoms of the disease, and the efficacy of the drug may decrease due to the formulation. .

In addition, if the formulation is used to fix and coat the drug without incorporating the drug into the above-mentioned base,
Sponge bases have poor physical strength and are porous, making it easy for drugs to diffuse out and leak, while tablet bases are rigid, which limits the areas where they can be applied. There is.

On the other hand, there are almost no preparations available for protecting damaged areas of the oral mucosa from external stimuli, and only tablets made of water-soluble polymer substances have been used.

However, as mentioned above, tablets have a problem in that their rigidity limits the areas to which they can be applied.

That is, a flexible and strong sheet-like dosage form is essential in order to cover and protect a wide area of the oral mucosa, etc., which is highly stretchable and has a complex shape.

In view of the state of the prior art, the present inventors have
The present invention was developed as a result of extensive research aimed at creating a mucosal bandage that overcomes these drawbacks.

That is, the mucosal bandage according to the present invention comprises (a) one or more of acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof, which are pharmaceutically safe materials, and (b) sodium carboxymethyl cellulose. By using a material consisting of one or more of sodium alginate or hydroxyethylcellulose, and (c) one or more of glycerin or propylene glycol, a flexible sheet or film that exhibits excellent adhesion to wet surfaces can be obtained; (d) One or more types of acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof; (e) One or more types of sodium carboxymethyl cellulose or hydroxyethyl cellulose; (f) One or more types of glycerin or propylene glycol; (g) A sheet or film that is flexible and strong can be obtained by using a material consisting of one or more pharmaceutically acceptable divalent or higher metal salts, and a sheet that is a combination of the two. Alternatively, if the film is applied to moist mucous membranes such as the oral cavity,
It has been found that the drug can be strongly adhered to the mucous membranes to provide a fixed coating of the drug, and that it does not irritate injured areas and has a good feeling of use.

That is, this invention provides an adhesion layer containing as an essential component one or more materials selected from the above (a), (b), and (c), and the above-mentioned (d), (e), (f), and ( The object of the present invention is to provide a mucosal bandage comprising a support layer containing as an essential component one or more of the materials selected from g).

Therefore, the blending amount of one or more of the acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof used in (a) and (d) in this invention may be determined by the type of polymer, molecular weight, or target. Although it varies depending on the physical properties of the formulation, both the adhesion layer and the support layer should be used in an amount of 1 to 50% by weight, especially 5 to 50% by weight of the total mixed solution.
35% by weight is preferred.

In addition, the blending amount of one or more of sodium carboxymethyl cellulose, sodium alginate, or hydroxyethyl cellulose in (b) is preferably 5 to 50% by weight, especially 15 to 35% by weight of the entire material forming the adhesive layer, and is preferably used in forming the support layer. (E) in the material
The same applies to the blending amount of one or more types of sodium carboxymethyl cellulose or hydroxyethyl cellulose.

Furthermore, the amount of one or more types of glycerin or propylene glycol in (c) and (f) is 30 to 90% by weight, particularly 50 to 90% by weight of the entire material forming the adhesion layer and the support layer, respectively.
80% by weight is suitable.

The blending amount of one or more pharmaceutically acceptable divalent or higher valent metal salts (g) used as one of the supporting layer forming materials is preferably 0.3 to 15% by weight, particularly 1 to 8% by weight.

Examples of pharmaceutically acceptable metal salts with a valence of two or more include calcium salts such as calcium chloride and calcium lactate, magnesium salts such as magnesium chloride and magnesium sulfate, aluminum salts such as aluminum chloride and alum, ferric chloride, Examples include iron salts such as iron citrate, and among them, calcium salts or magnesium salts are particularly preferred since the physical properties of the support layer can be easily controlled.

Since the mucosal bandage of the present invention essentially contains a water-soluble portion, if the mucosal bandage dissolves quickly during use and there is a risk that it will not stay on the mucosal surface sufficiently, it is necessary to add water to the supporting layer surface. Additionally, a non- or delayed water-soluble flexible film layer may be provided.

Furthermore, it is optional to add coloring agents, flavoring agents, etc. to the mucosal bandage of the present invention.

As detailed above, the mucosal bandage of the present invention is composed of a flexible adhesive layer that exhibits excellent adhesion to wet surfaces and a flexible and strong support layer, so it is suitable for use on complex surfaces such as oral mucosa. It has the characteristic of exhibiting excellent adhesion to mucous membranes that have a specific shape, and since the main ingredient is highly safe, it protects damaged areas without causing any irritation even when covered. It is possible.

This will be explained in detail below using examples.

Example 1 2 g of polyacrylic acid, 3 g of hydroxyethyl cellulose, 45 g of propylene glycol and 50 g of water
The mixed solution consisting of g was sufficiently stirred and mixed, and the mixed solution was applied onto the surface of a polyester film so that the thickness after drying was 200 μm, and dried to obtain an adhesive layer.

On the other hand, 1 g of carboxyvinyl polymer, 4 g of sodium carboxymethyl cellulose, 45 g of propylene glycol, and 0.3 g of calcium chloride. , 50g water
The aqueous solution was coated on another polyester film to a dry thickness of 100 μm, and dried to obtain a support layer.

The resulting support layer was peeled off from the polyester film surface and bonded onto the previously obtained adhesive layer via the peeled surface to obtain a mucosal bandage of the present invention.

The thus obtained mucosal bandage was peeled off from the polyester film surface at its adhesive layer and used on the oral mucosal surface of 10 panelists.
Good adhesion was achieved over 10 minutes.

Example 2 A 10% by weight aqueous solution of magnesium chloride was applied to the surface of the adhesive layer obtained in Example 1 and dried to transform the surface layer of the adhesive layer into a support layer to obtain a mucosal bandage.

When this mucosal bandage was measured in the same manner as in Example 1, it adhered well for an average of 10 minutes.

Example 3 Sodium polyacrylate 10g, sodium carboxymethylcellulose 10g, glycerin 26
g and 54 g of water were thoroughly stirred and mixed, and this mixed solution was applied onto the surface of a polyester film so that the thickness after drying would be 200 μm, and dried to obtain an adhesive layer.

On the other hand, 1.5 g of sodium polyacrylate, 0.6 g of sodium carboxymethyl cellulose, 17.5 g of glycerin, 0.8 g of calcium chloride, and 74.2 g of water.
The mixed solution consisting of g is sufficiently stirred and mixed, and this aqueous solution is applied onto the adhesion layer to a thickness of 100 μm after drying, and dried to form a support layer, thus producing the mucosal bandage of the present invention. I got it.

When this mucosal bandage was subjected to an application test in the same manner as in Example 1, it adhered well for an average of 15 minutes.

Example 4 Collodion (Japanese Pharmacopoeia) was applied to the adhesive layer surface of the mucosal bandage obtained in Example 3, and dried to form a non-dissolvable film layer to obtain a mucosal bandage.

When this mucosal bandage was subjected to an application test in the same manner as in Example 1, it adhered well for an average of 60 minutes.

Example 5 Ferric chloride 5 was applied to the surface of the adhesion layer obtained in Example 3.
A mucosal bandage was obtained by applying a wt % aqueous solution and drying to transform the surface layer of the adhesive layer into a support layer.

When this mucosal bandage was subjected to the same application test as in Example 1, it adhered well for an average of 20 minutes.

Example 6 A mixture of 25 g of sodium polyacrylate, 30 g of sodium alginate, and 45 g of glycerin and a mixture of 10 g of sodium polyacrylate, 36.5 g of hydroxyethyl cellulose, 45 g of glycerin, and 8.5 g of calcium chloride were molded into two layers. Thickness by pouring and heating compression molding
A 300 μm mucosal dressing was obtained.

When this mucosal bandage was subjected to the same application test as in Example 1, it adhered well for an average of 12 minutes.

Claims (1)

[Scope of Claims] 1 (a) The amount of one or more of acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof is 1 to 50% by weight, and (b) Sodium carboxymethyl cellulose, sodium alginate, or The amount of one or more types of hydroxyethyl cellulose is 5 to 50% by weight
(c) An adhesive layer containing 30 to 90% by weight of at least one type of glycerin or propylene glycol as an essential main component; and (d) an acrylic acid polymer, an acrylic acid copolymer, or their water-soluble properties. The amount of one or more types of salt is 1
~50% by weight, (e) The amount of one or more types of sodium carboxymethyl cellulose or hydroxyethyl cellulose is 5-50% by weight, (f) The amount of one or more types of glycerin or propylene glycol is 30-90% by weight, (g) A sheet-like or film-like mucous membrane characterized by comprising a support layer whose essential main ingredient is one or more pharmaceutically acceptable divalent or higher metal salts in an amount of 0.3 to 15% by weight. bandage. 2. The mucosal bandage according to claim 1, wherein the pharmaceutically acceptable divalent or higher metal salt is a calcium salt or a magnesium salt. 3 Among the essential components of the adhesive layer constituting the mucosal bandage, (a) the amount of one or more of acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof is 5%.
~35% by weight, (b) 15 to 35% by weight of one or more of sodium carboxymethylcellulose, sodium alginate or hydroxyethyl cellulose, (c) 50 to 80% by weight of one or more of glycerin or propylene glycol. A mucosal bandage according to claim 1 or 2, characterized in that: 4. Among the essential main components of the supporting layer constituting the mucosal bandage, (d) the amount of one or more of acrylic acid polymers, acrylic acid copolymers, or water-soluble salts thereof is 5.
~35% by weight, (e) 15 to 35% by weight of one or more of sodium carboxymethyl cellulose or hydroxyethyl cellulose, (f) 50 to 80% by weight of one or more of glycerin or propylene glycol (g) 2 The blending amount of one or more types of metal salts of 1 to 1
8% by weight of the mucosal bandage according to claim 1 or 2.