JPH059412B2 - - Google Patents

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention aims to treat gingivitis and alveolar abscess by applying a water-soluble film containing at least one of lysozyme chloride and allantoin and other drugs directly to the affected area in the oral cavity. This invention relates to a patch for gingivitis and alveolar pyorrhea containing lysozyme chloride that alleviates various symptoms associated with leakage and leads to recovery.

(Prior art) Conventionally, drugs used to treat periodontal diseases such as gingivitis and pyorrhea include ointments, powders, and creams that are applied to the affected area and used as a massage, and drugs that are placed in the oral cavity and dissolved. There is a tablet that lets you do it.

Furthermore, as a patch or something similar,
A preparation consisting of an integrated film-like adherent and a flexible film-like support, and containing a topical drug in at least one of the film-like adherent and the film-like support, wherein the film-like adherent is made of polyester. Oral preparation composed of a flexible film-like material in which at least one of carboxylic acid and carboxylic acid anhydride and vinyl acetate polymer are in a compatible state (Japanese Patent Application Laid-Open No. 62-255417), flexibility A drug layer composition is formed by laminating a drug layer composition in the form of a sheet on which a drug is blended into a composition mainly consisting of one or more water-soluble or water-swellable polymeric substances on a certain support. Gingival mucosa patch (Japanese Patent Application Laid-open No. 58-213709), which has a Young's modulus of 10 to 250 Kg/ _mm2 at 25°C and 65% relative humidity, and a viscosity of 2% aqueous solution of 5 to 30,000 centipoise at 20°C. There are film-shaped or sheet-shaped preparations for periodontal disease treatment that are inserted into periodontal pockets or gingival regions and are made of a water-soluble polymer substance and a drug for periodontal disease treatment (Japanese Patent Application Laid-Open No. 59-222406). Are known.

(Problems to be Solved by the Invention) Among the various formulations mentioned above, the dosage forms such as ointments, drops, and creams are easily dissolved by saliva or body temperature within a short period of time, so they are not dispersed in the oral cavity or swallowed. The long-term medicinal effect cannot be expected. Furthermore, since the amount of each application varies, it is difficult to administer a constant amount.

On the other hand, since Vatukaru tablets are tablets, they can improve the problems of maintaining drug efficacy and specifying dosage, but because they are used by dissolving them in the vestibule of the oral cavity, it is difficult to have an accurate effect on the affected area. Certain medicinal effects may not be expected. Another problem is that since it is just over 1 mm thick, it feels uncomfortable when placed in the oral cavity, making it difficult to use.

The above-mentioned problems have been considerably improved with adhesive patches or similar products, but in the preparation of the invention of JP-A No. 62-255417, the base polycarboxylic acid or polycarboxylic anhydride is substantially dissolved by vinyl acetate polymer. Since it is completely water-insoluble, it remains attached for an extremely long time. And adhesion test (immersion in water)
It remained firmly attached even after 5 hours. Although it is preferable for the film to remain stuck for a long time in terms of effective absorption of the drug, it is not preferable for the film to remain stuck in the oral cavity for a long time, even though it is thin, because of the feeling of a foreign body. Since it does not dissolve, it needs to be removed at an appropriate time, but the timing of removal is a problem because it is not known how much of the main drug has been absorbed.

The formulation of the invention disclosed in JP-A No. 58-213709 does not have the risk of being dissolved and disintegrated by saliva and swallowed, but it remains on the gums for a long time (several to 20 hours), so it does not feel like a foreign body. This is not desirable, or it is troublesome as it requires removal. Furthermore, since the support is not edible, there are problems if the product is swallowed.

Since the preparation of the invention of JP-A No. 59-222406 is inserted into the periodontal pocket or the bottom of the gingiva and is not used as a patch, there is no need to give much consideration to adhesive strength, so it can be used as a patch preparation. is not appropriate. Since it is inserted into periodontal pockets, the hardness must be appropriate; if it is too soft, it will not fit properly, and if it is too hard, it will cause pain, so adjusting the hardness is troublesome. Furthermore, it is necessary to measure the Young's modulus and viscosity of the water-soluble polymer substances used, which is troublesome.

(Means for solving the problem) As a result of consideration, we found that since the affected area is located in a position that is difficult to see from the outside, it is possible to cover a relatively wide area, and that it adheres to the affected area and does not fall off easily.
Since this is a sensitive area, it was necessary to have a form and property that would cause as little discomfort as possible, and we therefore determined that a film-like patch would be appropriate. We have come to the conclusion that it is preferable for the formulation itself to dissolve gradually (in terms of discomfort, etc.).

The drug contained in the film-like patch must have bacteriolytic, hemostatic, and strong anti-inflammatory effects, and must be particularly effective in preventing and inhibiting the progression of periodontal disease. Lysozyme chloride was found to be the most suitable. Lysozyme chloride is a mucopolysaccharide-degrading enzyme and is a valuable anti-inflammatory enzyme that has bacteriolytic action against bacteria, anti-inflammatory action against carrageenan edema, etc., as well as tissue repair action and hemostatic action.

In addition, allantoin, hinokitiol, peppermint oil, tocopherol acetate, chamomile tincture,
Cetylpyridinium chloride, chlorhexidine hydrochloride, ethyl aminobenzoate, dibucaine hydrochloride, hexothiocaine hydrochloride, dequalinium chloride, glycyrrhetinic acid, dipotassium glycyrrhizinate, thymol, benzalkonium chloride, diphenhydramine salicylate, nitrofurazone, tecitodecitin, sodium/calcium edetate , phenol, copper chlorophyllin sodium, and sodium chloride, and at least one lysozyme chloride selected from the group consisting of lysozyme chloride. The film layer, that is, the drug-containing layer is composed of a rapidly dissolving layer and a slow dissolving layer,
Furthermore, by arranging a non-adhesive support layer made of an enteric polymer substance on the slow dissolution layer side,
The present inventors have discovered that it is possible to obtain a patch that is both fast-acting and has appropriate durability, and has completed the present invention.

That is, the object of the present invention is to provide lysozyme chloride, allantoin, hinokitiol, peppermint oil, tocopherol acetate, chamomile tincture, cetylpyridinium chloride, chlorhexidine hydrochloride, ethyl aminobenzoate, dibucaine hydrochloride, hexothiocaine hydrochloride, dequalinium chloride, glycyrrhetinic acid, glycyrrhizic acid Dipotassium, thymol, benzalkonium chloride, diphenhydramine salicylate,
A water-soluble film layer that is adhesive to the oral mucosa and contains at least one member selected from the group consisting of nitrofurazone, tecitodecitin, sodium/calcium edetate, phenol, copper chlorophyllin sodium, and sodium chloride, and a non-adhesive intestine. An object of the present invention is to provide a patch for gingivitis and alveolar pyorrhea, which is a patch consisting of a soluble film (support layer), the water-soluble film layer comprising a rapidly dissolving layer and a slow dissolving layer. .

Among allantoin and other drugs used as an adjunct in the present invention, allantoin is abundant in the juice obtained by crushing the underground roots of perennial plants that occur in wetlands, and is used to remove necrotic tissue (or mackerel debris). It is especially useful because it has an exfoliating effect and at the same time has a medicinal effect that promotes the recovery of bad periodontal tissue to new normal tissue. In the present invention, the amount of lysozyme chloride used is 0.01 to 10% by weight.
The appropriate amount of allantoin and other drugs used is 0.01 to 10% by weight.

In the present invention, it is essential that lysozyme chloride, allantoin, and other active ingredients are uniformly mixed and dispersed in a water-soluble film, and the purpose of the present invention cannot be achieved simply by coating or embedding them in the same film. .

In the present invention, the water-soluble film and enteric film must be edible. A water-soluble film is composed of a water-soluble polymer compound, and refers to a film that mainly dissolves in the oral cavity and stomach. Specifically, polyvinylpyrrolidone (hereinafter referred to as PVP),
Gelatin, polyvinyl alcohol, sodium polyacrylate, sodium carboxymethylcellulose, starch, xanthan gum, karaya gum, sodium alginate, methylcellulose,
Examples include carboxyvinyl polymer, agar, and hydroxypropylcellulose, and the water-soluble film is mainly composed of at least one of these. Among the above, regarding hydroxypropyl cellulose, both high viscosity hydroxypropyl cellulose (hereinafter referred to as HPC-H) and low viscosity hydroxypropyl cellulose (hereinafter referred to as HPC-L) may be appropriately used depending on their properties.

Polymer compounds constituting the enteric film include hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, carboxymethylethylcellulose, shellac, and methacrylic acid ethyl acrylate copolymer (this is an emulsion). easy to use)
can be used. In addition, it is recommended to use shellac together with other enteric substances.

It is better not to make the formulation of the present invention too thick in order to avoid discomfort. Specifically, the thickness of the water-soluble film is determined based on the balance between the dissolution rate of the water-soluble film, the duration of its medicinal efficacy, and discomfort. In other words, if it is too thin, it will dissolve too quickly, depending on the polymer compound used.
20μm or more is better. On the other hand, although the maximum thickness varies from person to person, it is preferably 300 μm or less, and if it is more than that, most people will feel uncomfortable. In addition, the thickness of the enteric film layer, that is, the support layer is 5~
20 μm is appropriate.

In order to uniformly contain lysozyme chloride, allantoin, and other active ingredients in a thin film and control the thickness, it is important to select a solvent that can dissolve or mix and disperse the ingredients and a substance that can form a thin film. It is.

In the present invention, since the preparation is used in the oral cavity and enters the body, it is a matter of course that it must not have any harmful effects on the human body. In addition, since the solvent is distilled off after spreading, it is necessary to use a solvent that has a relatively low specific heat and that can dissolve the required amount of drugs, etc. in as small an amount as possible in terms of solvent distillation. It won't happen.

As a result of considering the above points, the solvent for the patch of the present invention was limited to water, ethanol, and methylene chloride.
This allows the water-soluble film layer to be 20 to 300 μm thick.
It has been possible to advantageously obtain a useful patch having an enteric film layer thickness of 5 to 20 μm, which can maintain its medicinal efficacy and exhibit a sufficient therapeutic effect.

When preparing the patch of the present invention, macrogol 400, propylene glycol, glycerin, etc. may be used as plasticizers for water-soluble films and enteric films. Water or ethanol may be used as a solvent for preparing a water-soluble film. In addition, ethanol is used as a solvent for preparing enteric film.
It is preferable to use a mixture of ethanol and water, or a mixture of ethanol and methylene chloride (1:1 is suitable). Incidentally, a coloring agent and other substances may be added as desired during preparation.

In the patch of the present invention, the active ingredients such as lysozyme chloride and allantoin are contained in a water-soluble film, so as this film dissolves in the oral cavity, the active ingredients such as lysozyme chloride are also applied. Acts directly on the affected area of the oral cavity. In particular, the water-soluble film of the present invention adapts to the shape of the application part as a whole and adheres to the oral mucosa, and exerts a medicinal effect directly on the affected area over the entire adhesion area. It is easy to apply the medicine to the affected area, and it is possible to accurately apply the medicinal effect to the affected area.

Since the water-soluble film layer consists of a fast-dissolving layer and a slow-dissolving layer, the fast-dissolving layer attached to the mucous membrane dissolves relatively quickly, giving it quick-acting properties. , then the slow dissolving layer gradually dissolves to provide persistence. Furthermore, the enteric film layer does not dissolve after a certain amount of time, but disintegrates into small pieces that can be swallowed as is, so it does not adhere to the mucous membrane for an unnecessarily long time and there is no problem in terms of discomfort.

(Effect of the invention) By containing lysozyme chloride, allantoin, etc. in this way, it is continuously effective in preventing and inhibiting the progression of periodontal disease due to its bacteriolytic, hemostatic, strong anti-inflammatory and tissue repair effects. In addition to promoting the recovery of normal tissue, the treatment effect for periodontal disease was enhanced.

(Example) Next, an example of the present invention will be shown, but the present invention is not limited thereto.

FIG. 1 shows a cross section of the patch according to the present invention, where 1 is a drug-containing layer, 1a is a rapidly dissolving film layer, 1b is a slow dissolving film layer, and 2 is an enteric film layer (supporting material). layer).

FIGS. 2, 3, and 4 show the elution curves of the patches of Reference Examples 1 and 2 and Examples 1 to 5 containing lysozyme chloride and allantoin and other drugs. As a result, the enteric film 2, which is a non-adhesive layer,
It is understood that the dissolution rate from the adhesive layer does not exceed 10% even after 4 hours, and on the other hand, the dissolution rate from the adhesive layer to the affected area is remarkable and acts in a sustained manner. Note that this elution characteristic is based only on lysozyme chloride, but even if allantoin or the like is also included, the elution characteristics of these active ingredients are the same as in the case of lysozyme chloride.

(Reference example 1) Enteric film (non-adhesive layer); methacrylic acid ethyl acrylate copolymer (emulsion) 90
Parts by weight and 10 parts by weight of Macrogol 400 were uniformly mixed, and after being spread and dried, an enteric film having a thickness of about 10 μm was formed.

Soluble film (adhesive layer); lysozyme chloride 10
parts by weight, allantoin 5 parts by weight, macrogol
400 and 10 parts by weight of glycerin are uniformly mixed or dissolved in 100 parts by weight of water, and HPC-H50
15 parts by weight of HPC-L were mixed and dissolved in 1000 parts by weight of ethanol, mixed uniformly with the solution, and after being spread and dried on an enteric film, a soluble film having a thickness of about 150 μm was formed.

A laminated (two-layer) film having a thickness of 160 μm was formed using the above enteric film and the soluble film.

(Reference Example 2) Enteric film (non-adhesive layer): Formed in the same manner as in Reference Example 1.

Soluble film (adhesive layer); lysozyme chloride 5
parts by weight, allantoin 5 parts by weight, macrogol
Uniformly mix or dissolve 10 parts by weight of 400 in 100 parts by weight of water, and also add 50 parts by weight of PVP, 10 parts by weight of HPC-H,
20 parts by weight of HPC-L was mixed and dissolved in 1000 parts by weight of ethanol, mixed uniformly with the solution, and after being spread and dried on an enteric film, a soluble film having a thickness of 50 μm was formed.

A laminated (two-layer) film with a thickness of approximately 60 μm was formed using the above enteric film and the soluble film.

(Example 1) Enteric film (non-adhesive layer); methacrylate ethyl acrylate copolymer (emulsion) 90
Parts by weight and 10 parts by weight of Macrogol 400 were uniformly mixed, and after being spread and dried, an enteric film with a thickness of about 10 μm was formed.

Delayed dissolution film (intermediate layer with adhesive properties): 10 parts by weight of lysozyme chloride, 5 parts by weight of allantoin
Parts by weight, Macrogol 400 10 parts by weight, Glycerin
Uniformly mix or dissolve 10 parts by weight in 100 parts by weight of water,
In addition, 50 parts by weight of HPC-H and 15 parts by weight of HPC-L were mixed and dissolved in 1000 parts by weight of ethanol, mixed uniformly with the above solution, and spread and dried on an enteric film to form a slow-dissolving film with a thickness of about 150 μm. Formed.

Rapidly dissolving film (adhesive layer): 5 parts by weight of lysozyme chloride, 5 parts by weight of allantoin, 10 parts by weight of Macrogol 400 are uniformly mixed or dissolved in 100 parts by weight of water, and 50 parts by weight of PVP, 10 parts by weight of HPC-H. , 20 parts by weight of HPC-L was mixed and dissolved in 1000 parts by weight of ethanol, mixed uniformly with the solution, and spread on a slow dissolving film spread on an enteric film to a thickness of about 50 μm after drying. A rapidly dissolving film was formed.

A laminated (three-layer) film having a thickness of about 210 μm was formed from the enteric film, slow dissolving film, and fast dissolving film described above.

(Example 2) Enteric film (non-adhesive layer); 90 parts by weight of carboxymethylethylcellulose, 400 parts by weight of macrogol
7 parts by weight and 3 parts by weight of shellac were uniformly mixed or dissolved in 1000 parts by weight of ethanol, and after being spread and dried, the thickness was approx.
A 5 μm enteric film was formed.

Slow dissolution film (intermediate layer with adhesive properties): 15 parts by weight of lysozyme chloride, 5 parts by weight of allantoin
parts by weight, 2 parts by weight of cetylpyridinium chloride in water
Uniformly mixed or dissolved in 100 parts by weight, HPC
-H60 parts by weight, HPC-L10 parts by weight, glycerin 8
Parts by weight were uniformly mixed or dissolved in 1000 parts by weight of ethanol, and the mixture was uniformly mixed with the above solution to form a slow-dissolving film with a thickness of about 200 μm after being spread and dried on an enteric film.

Rapidly dissolving film (adhesive layer): 5 parts by weight of lysozyme chloride, 5 parts by weight of allantoin, 2 parts by weight of cetylpyridinium chloride are uniformly mixed or dissolved in 100 parts by weight of water, and 60 parts by weight of HPC-L, 20 parts by weight of propylene glycol. parts by weight, 8 parts by weight of glycerin are uniformly mixed or dissolved in 1000 parts by weight of ethanol,
After being spread and dried, a rapidly dissolving film having a thickness of about 50 μm was formed on the slow dissolving film which was uniformly mixed with the above solution and spread on an enteric film.

A laminated (three-layer) film having a thickness of about 255 μm was formed from the enteric film, slow dissolving film, and fast dissolving film described above.

(Example 3) Enteric film (non-adhesive layer): 85 parts by weight of hydroxypropyl methylcellulose phthalate, 13 parts by weight of Macrogol 400, and 2 parts by weight of titanium oxide were uniformly mixed into 300 parts of ethanol/water (8:2) or After dissolving, spreading and drying, an enteric film with a thickness of about 10 μm was formed.

Delayed dissolution film (adhesive intermediate layer): 5 parts by weight of lysozyme chloride, 5 parts by weight of allantoin
Parts by weight, 2 parts by weight of peppermint oil, and 10 parts by weight of sodium chloride were uniformly mixed or dissolved in 100 parts by weight of water, and 30 parts by weight of HPC-H, 30 parts by weight of HPC-L, 10 parts by weight of carboxyvinyl polymer, and 8 parts by weight of glycerin were added.
Parts by weight were uniformly mixed or dissolved in 1000 parts by weight of ethanol, and the mixture was uniformly mixed with the above solution, spread and dried on an enteric film to form a slow-dissolving film with a thickness of about 200 μm.

Rapidly dissolving film (adhesive layer): 5 parts by weight of lysozyme chloride, 5 parts by weight of allantoin, 2 parts by weight of peppermint oil
parts by weight, 10 parts by weight of sodium chloride are uniformly mixed or dissolved in 100 parts by weight of water, 40 parts by weight of PVP, HPC
- 20 parts by weight of L, 8 parts by weight of glycerin, and 10 parts by weight of Macrogol 400 are uniformly mixed or dissolved in 1000 parts by weight of ethanol, and the mixture is uniformly mixed with the solution and spread on an enteric film. After spreading and drying, a rapidly dissolving film with a thickness of about 30 μm was formed.

Enteric-coated films, slow-dissolving films,
A laminated (three-layer) film having a thickness of approximately 240 μm was formed using a rapidly dissolving film.

(Example 4) Enteric film (non-adhesive layer); Hydroxypropyl methyl cellulose acetate succinate 85
parts by weight, 3 parts by weight of shellac were mixed and dissolved in 400 parts by weight of ethanol/methylene chloride (1:1), and 10 parts by weight of Macrogol 400 and 2 parts by weight of titanium oxide were mixed and dissolved or dispersed in 100 parts by weight of water. , was uniformly mixed with the above solution, and after being spread and dried, an enteric film with a thickness of 10 μm was formed.

Delayed dissolution film (intermediate layer with adhesive properties): 10 parts by weight of lysozyme chloride, 5 parts by weight of allantoin
parts by weight, 5 parts by weight of dipotassium glycyrrhizinate are uniformly mixed or dissolved in 100 parts by weight of water, and
50 parts by weight of HPC-H, 10 parts by weight of HPC-L, 10 parts by weight of glycerin, and 10 parts by weight of Macrogol 400 are uniformly mixed or dissolved in 1000 parts by weight of ethanol, mixed uniformly with the solution, spread and dried on an enteric film. A slow-dissolving film with a thickness of about 200 μm was then formed.

Rapidly dissolving film (adhesive layer): 5 parts by weight of lysozyme chloride and 5 parts by weight of allantoin were uniformly dissolved in 100 parts by weight of water, and 60 parts by weight of HPC-L,
Uniformly mix or dissolve 20 parts by weight of propylene glycol and 10 parts by weight of glycerin in 1000 parts by weight of ethanol, mix uniformly with the solution, spread and dry on the slow dissolving film spread on the enteric film. A rapidly dissolving film with a thickness of about 30 μm was then formed.

Above, enteric coated film, slow dissolving film,
A laminated (three-layer) film having a thickness of approximately 240 μm was formed using a rapidly dissolving film.

(Example 5) Enteric film (non-adhesive layer): 90 parts by weight of cellulose acetate phthalate and 10 parts by weight of Macrogol 400 were uniformly mixed with 200 parts by weight of ethanol/methylene chloride (1:1), spread and dried. An enteric film with a thickness of about 5 μm was formed.

Delayed dissolution film (intermediate layer with adhesive properties): 10 parts by weight of lysozyme chloride, 5 parts by weight of allantoin
5 parts by weight of sodium chloride were dissolved in 100 parts by weight of water, and 30 parts by weight of HPC-H, 5 parts by weight of HPC-
30 parts by weight of L, 10 parts by weight of carboxyvinyl polymer, 10 parts by weight of Macrogol 400, 1000 parts by weight of ethanol
It is uniformly mixed or dissolved in parts by weight, mixed uniformly with the solution, spread on an enteric film, and after drying, a thickness of approximately
A slow dissolving film of 250 μm was formed.

Rapidly dissolving film (adhesive layer); 5 parts by weight of lysozyme chloride, 5 parts by weight of allantoin, and 5 parts by weight of sodium chloride were dissolved in 100 parts by weight of water, and
50 parts by weight of PVP, 25 parts by weight of HPC-L, and 10 parts by weight of Macrogol 400 are uniformly mixed or dissolved in 1000 parts by weight of ethanol, and the mixture is uniformly mixed with the above solution to form a slow-dissolving film spread on an enteric film. After spreading and drying, a rapidly dissolving film with a thickness of about 10 μm was formed on top.

A laminated (three-layer) film with a thickness of about 265 μm was formed from the enteric film, slow dissolving film, and fast dissolving film described above.

The patches for gingivitis and alveolar pyorrhea containing lysozyme chloride and other drugs described above in Examples 1 to 5 adhere well to the periodontal affected area and cover a wide area, making them ideal for application inside the oral cavity. The desired effect was achieved without causing any discomfort.

[Brief explanation of the drawing]

The drawings relate to the patch for gingivitis and alveolar pyorrhea containing lysozyme chloride according to the present invention; FIG. 1 is a cross-sectional view of the patch, and FIGS. 2, 3, and 4 show the elution characteristics of lysozyme chloride. It is a graph.

Claims (1)

[Scope of Claims] 1 Lysozyme chloride and allantoin, hinokitiol, peppermint oil, tocopherol acetate, chamomile tincture, cetylpyridinium chloride, chlorhexidine hydrochloride, ethyl aminobenzoate, dibucaine hydrochloride, hexothiocaine hydrochloride, dequalinium chloride, glycyrrhetinic acid, dipotassium glycyrrhizinate , thymol, benzalkonium chloride, diphenhydramine salicylate, nitrofurazone, tecitodecitin, sodium/calcium edetate, phenol, sodium copper chlorophyllin, and sodium chloride. In a patch consisting of a water-soluble film layer having adhesive properties and a non-adhesive enteric film layer (supporting layer), the water-soluble film layer is composed of a rapid dissolving layer and a slow dissolving layer. A patch for gingivitis and alveolar pyorrhea containing lysozyme chloride. 2. The water-soluble film is selected from the group consisting of polyvinylpyrrolidrine, gelatin, polyvinyl alcohol, sodium polyacrylate, sodium carboxymethylcellulose, starch, xanthan gum, karaya gum, sodium alginate, methylcellulose, carboxyvinyl polymer, agar, and hydroxypropylcellulose. The patch for gingivitis and alveolar pyorrhea containing lysozyme chloride according to claim 1, which comprises at least one water-soluble polymer. 3. The enteric film contains at least one type of enteric film selected from the group consisting of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, carboxymethyl ethyl cellulose, shellac, and methacrylic acid ethyl acrylate copolymer. A patch for gingivitis and alveolar pyorrhea containing lysozyme chloride according to claim 1 or 2, which comprises a molecular compound. 4 Lysozyme chloride 0.2% to 20% by weight, allantoin and other drugs 0.01% to 10% by weight
A patch for gingivitis and alveolar pyorrhea containing lysozyme chloride according to any one of claims 1 to 3. 5. Lysozyme chloride-containing gingivitis/dental alveolus according to any one of claims 1 to 4, wherein the water-soluble film layer has a thickness of 20 to 300 μm and the enteric film layer has a thickness of 5 to 20 μm. Patch for pyorrhea.