JPH0259513A - Oral cavity mucosa-attaching type halitosis-preventing agent - Google Patents

Abstract

PURPOSE:To provide the subject agent having remarkable odor-modifying, taste- modifying and deodorizing actions, preventing halitosis and having fast-acting and persisting properties without a feeling of physical disorder by comprising a water-soluble film which contains an active ingredient having a halitosis- preventing effect and is attached to an oral mucosa. CONSTITUTION:The subject agent comprises a water-soluble film which contains an active ingredient having a halitosis-preventing effect and is attached to an oral mucosa. The active ingredient is selected from l-menthol, dl-camphor, peppermint oil, fennel fruit oil, gambir-catechu, etc., which exhibit mainly taste- modifying and odor-modifying, the content of the active ingredient being 0.1-5wt.%. A compound exhibiting the deodorizing effect includes flavonoid, cetylpyridinium chloride, etc., and the content of the compound is preferably 0.01-5wt.%. These active ingredients are preferably mixed and dispersed in a water-soluble film such as gelatin film and the thickness of the film is preferably 15-330mum.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to an oral mucosal adhesive type anti-halitosis agent that can eliminate bad breath by directly applying it to the oral cavity.

(Prior Art) Conventionally used formulations of anti-halitosis agents include liquids, powders, sprays, lozenges, and gunpowders. Liquid preparations and powder preparations have the disadvantage of being difficult to dispose of after oral irrigation, and cannot be used anytime and anywhere. Sprays, lozenges, and gun powder are easy to carry and use, but sprays are not persistent. In addition, lozenges and gunpowder have the disadvantage that they have an unpleasant sensation, hinder conversation, etc., are easily chewed or swallowed, and are less effective. For the above reasons, conventional products cannot be expected to be sustainable.

(Technical Issue) Therefore, the present inventors conducted extensive research to determine what kind of dosage form would be optimal for this type of use. In addition, since it is a sensitive area, it is necessary that the shape and properties cause as little discomfort as possible, and that it is long-lasting and has sustained release properties.
A film-like adhesive patch satisfies this condition.

In addition, the active ingredient for preventing bad breath contained in the film-like patch must exhibit taste-correcting, odor-correcting, and deodorizing effects.

Therefore, the object of the present invention is to provide an effective composition for preventing bad breath.

An object of the present invention is to provide a sustained-release oral mucosal patch-type halitosis preventive agent, which is a film-like adhesive patch containing at least a water-soluble film, and which releases an active ingredient while dissolving.

(Technical means) The purpose is to contain an active ingredient having an anti-halitosis effect,
This is achieved by an oral mucosal adhesive type anti-halitosis agent made of a water-soluble film that adheres to the oral mucosa.

Active ingredients include (-menthol, d-camphor, peppermint oil, fennel oil, acaenia oil, and camphor.

Selected from elephant, chlorophyllin derivatives, cinnamon bark, koshiyo, shukusha, ginger, clove, chili pepper, U-men 1-le, hyakuso, mokko, yakuchi, rhyuno, nikuzuku, ginger oil, cinnamon bark oil, saffron, rose oil, matcha It is possible to contain one or more of the following. These mainly exert flavor correction and odor correction effects, and the content ratio of each active ingredient is from 0.1 to ff1ffi ratio.
5%.

Other active ingredients include 1 selected from flavonoids, cetylpyridinium chloride, 1JlliQ chlorhexidine, dequalinium chloride, and chlorhexidine gluconate.
A species or two or more species can be included. These mainly exhibit a deodorizing effect, and the content ratio of each active ingredient is preferably 0.01 to 5% by weight. This is because if it is less than 0.1% or 0.01%, respectively, it is too dilute and the desired halitosis prevention effect cannot be obtained, and if it exceeds 5%, no improvement in the effect can be expected. Note that there is no pharmacological problem between active ingredients that primarily have flavor-correcting and odor-correcting effects and active ingredients that primarily have deodorizing effects.

They can be used together as long as possible (Claim 4).

It is essential that the above-mentioned effective ingredients for preventing bad breath are uniformly mixed and dispersed in a water-soluble film, and the object of the present invention cannot be achieved simply by coating or embedding them in the film.

The water-soluble film mainly refers to a film that dissolves in the oral cavity and stomach. Water-soluble films include polyvinylpyrrolidone, gelatin, polygonyl alcohol, sodium polyacrylate, carbo-4-dimethylcellulose, starch, nanthanum gum karaya gum, sodium alginate, methylcellulose, carboxyvinyl polymer,
Examples include agar and hydroxypropyl cell (coase), and it is mainly composed of one or more of these.

As described above, it is necessary for the water-soluble film to be both edible and water-soluble, but this alone is not sufficient and the formulation must have a structure that does not become thick. 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 the sense of discomfort. If it is too thin, it will not dissolve quickly, although it depends on the film material, so the thickness is preferably 15 μm or more. Although the maximum thickness varies from person to person, it is preferably 400 .mu.m or less, more preferably 330 .mu.m or less in the form of a preparation; if it is more than that, many people will feel uncomfortable.

In order to uniformly contain the active ingredient in a thin film and control the thickness of the film, it is also important to select a solvent that can dissolve or mix and disperse the ingredients and the substance capable of forming a thin film.

Naturally, this type of solvent must not have any harmful effects on the human body since the preparation is used in the oral cavity and enters the body.

Furthermore, 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 drug with as little friction as possible in terms of solvent distillation.

As a result of considering the above points, the present invention limits the solvent to water, ethanol, and methylene chloride, and then selects the various components necessary to form the patch.
This made it possible to control the agent thickness to 15 to 330 μm.

In addition, water-soluble films are roughly divided into rapid-onset (immediate-onset) and delayed-onset films depending on the dissolution rate, and these films may be used alone or in appropriate combinations to constitute the base material of the halitosis preventive agent. be able to.

(Function) In the anti-halitosis agent of the present invention configured as described above, the active ingredient is contained in the water-soluble film, so as this film dissolves in the oral cavity, the active ingredient also dissolves in the water-soluble film. It spreads and acts throughout the oral cavity from the affected area.

In particular, the water-soluble film of the present invention adapts to the shape of the part to be applied and adheres to the oral mucosa, so it is more effective to reach the entire oral cavity than when a drug is embedded or applied to the film. early.

The synergistic effect of these structural main components and precise medicinal effects makes it possible to eliminate bad breath by quickly masking the odor and taste in the oral cavity with its odor-correcting action, or by its deodorizing action. Also fal
When the water-soluble film is constituted by the Fi film and the negative layer is a slow-dissolving film, the dissolution time is significantly extended, and as a result, the halitosis prevention effect continues for a long time.

(Effect) In order to objectively clarify the halitosis removing effect and sustainability of the present invention, analysis by gas chromatography was attempted. Methyl mercaptan is selected as a volatile malodorous substance thought to be included in bad breath, and after washing the inside of the oral cavity once with mouthwash, gargling with artificial halitosis 10ae for 1 minute, and immediately after spitting it out, administer each anti-halitosis agent. Bedspace gases in exhaled breath were analyzed over time by gas chromatography. The results are shown in the following table and Figure 6.

From the results of the residual rate (%) of methyl mercaptan over time, it was confirmed that all the products other than the present invention (Example 33) lost their effectiveness after about 20 minutes, and the artificial halitosis returned again. However, according to the present invention, 60% in 20 minutes
% of methyl mercaptan and remained so for 2 hours.

As described above, the product of the present invention has a structure in which the active ingredient is contained in a water-soluble film, and can prevent bad breath due to its remarkable odor correction, flavor correction and deodorization effects.Moreover, it is in the form of a thin film and has no oral adhesive properties. Because it was adhered to the skin, it did not cause any discomfort, and it exhibited excellent practical effects due to its immediate and long-lasting effect.

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

The drawing shows continuous dissolvable film 1 with a single layer of water-soluble film.
(FIG. 1), and one (FIG. 2) consisting only of a slow-dissolving single-layer film 2.

An example of a multilayer film consisting of both films 1.2 (Fig. 3) and a three-layer laminated film in which the continuous dissolution layer 1.1 is laminated to the outer layer of the slow dissolution film 2 in the center (Fig. 3). When both films 1 and 2 come into close contact with Oral Self-Sufficiency! (Figure 5).The rapid dissolving film is designed to provide an immediate effect, and the delayed dissolving film is provided to provide a sustained effect, but both films contain polyvinylpyrrolidone, gelatin, polyvinyl alcohol, sodium polyacrylate, carboxymethyl cellulose, Starch, xanthan gum, karaya gum, sodium alginate, methylcellulose,
It is composed of an intraorally soluble film made of one or more selected from carboxyvinyl polymer agar, hydroxypropyl cellulose, etc., and the dissolution time is adjusted depending on the ratio of each component.

Note that each active ingredient is contained throughout the film.

<Example 1) Continuously soluble film (adhesive layer): 2.5 parts by weight of °C-menthol, 2.0 parts by weight of mustard oil, and 1.0 parts by weight of fennel shown in Example 1 of Table 1 as active ingredients. 10 parts of hydroxybrobyl cellulose (1-IP C-H),
Hydroxypropylcellulose (HPC-L) 30 parts by weight, polyvinylpyrrolidone (PVP) 44.5ff
The lffi part was dissolved in 1,000 parts by weight of ethanol together with 10 parts by weight of macrogol 40010 as a plasticizer, and after being spread and dried, an oral mucosal adhesive type anti-halitosis agent consisting of a single-layer film with a thickness of about 122 μm was formed.

(Examples 2 to 8) Regarding those in which the active ingredients and film-forming ingredients were changed according to the component ratios shown in Examples 2 to 8 in Table 1,
An oral mucosal adhesive type anti-halitosis agent consisting of 714 I11 layer film was formed by the same method as in Example 1. Their thicknesses are shown in the bottom column of Table 1. However, Example 6
The solvent in Example 7 was changed to 1000 parts by weight of water, and the solvent in Example 7 was changed to 1000 parts by weight of methylene chloride. Note that Example 8.1
The chloro in 6 indicates a chlorophyllin derivative.

When the rapid dissolving film anti-halitosis agents shown in Examples 1 to 8 above were applied to the oral mucosa to evaluate their practicality, this group of anti-halitosis agents adhered to the entire oral mucosa without any discomfort. It exhibited the effect of eliminating bad breath without peeling until the end, and completely dissolved after about 30 to 40 minutes.

(Example 9) Slow-dissolving film (adhesive layer): The active ingredients are shown in Example 9 in Table 2 (-2.0 parts by weight of menthol, 2.0 parts by weight of mustard oil, 0.5 parts by weight of Wikimiu) , HPC-H
It was dissolved in 1000 parts by weight of ethanol together with 40 parts by weight and 35.5 parts by weight of HPC-L20 heavy hanging part PVP to form an oral mucosal adhesive type anti-halitosis agent consisting of a single layer film with a thickness of 25.4 μm after being spread and dried. .

(Examples 10 to 16) The active ingredients and film-forming ingredients were prepared according to Examples 10 to 16 in Table 2.
Using the same method as in Example 9, the oral mucosal adhesive type anti-halitosis agent consisting of seven types of single-layer films was formed using the same method as in Example 9, except for the compositions whose component ratios were changed according to the ratios shown in Example 16.

Their thicknesses are shown in the lower column of Table 2.

When the slow-dissolving film anti-halitosis agents shown in Examples 9 to 16 were applied to the oral mucosa to evaluate their practicality, this group of anti-halitosis agents also adhered to the entire oral mucosa surface without any discomfort. It exerts the effect of eliminating bad breath without exfoliating until the end,
It was completely dissolved after about 40 to 60 minutes.

(Examples 17 to 24) A mixture and solution mixed and dissolved according to the component ratio of Example 9 was spread on the continuously dissolvable film (adhesive layer) having a thickness of about 122 μm formed in Example 1, and after drying, a thickness of about 122 μm was spread. 25μm
A slow-dissolving film layer was formed. As a result of the above, the thickness of the continuous dissolving film and the slow dissolving film is approximately 147 cm.
A μm multi-layered oral mucosal adhesive type anti-halitosis agent was formed (3rd
table).

The following are the continuous dissolving film of Example 2 in Table 1 and the second
Approximately 1 thick of the slow dissolving film of Example 10 in the table
A 77 μm multilayer film of Example 8 and Example 16 was combined as shown in the upper row of Table 3 to form an oral mucosal adhesive type anti-halitosis agent.

The combination of ingredients and thickness of Examples 17 to 24 above are the same as those of the third embodiment.
It is shown in the upper right column of the table. When we evaluated the practicality of these multi-layer anti-halitosis agents by attaching them to the oral mucosa, we found that the time it took to exert the effect of eliminating bad breath was significantly prolonged, and it was confirmed that this time was proportional to the thickness of the agent. Ta. However, the material of Example 20 had a thickness of 396 μm based on the standard.
Some people complained of discomfort in the oral cavity because the diameter exceeded 30 μm.

(Examples 25 to 32) The rapid dissolving film of Example 1 was spread on both sides of the slow dissolving film of Example 9, and the total thickness of each film was approximately 269 μm, and 3FI was applied to the oral mucosa. A mold anti-halitosis agent was formed (Example 25).

In addition, a three-layer halitosis preventive agent was formed by combining the ingredients shown in the lower row of Table 3. This group of anti-halitosis agents had a significantly longer effective time than those in the previous two groups, with some lasting over an hour (Examples 27 and 28); was judged to be unsuitable.

(Examples 33 to 37) Examples of this group contain 5 seconds of flavonoid as an active ingredient with a deodorizing effect, and the water-soluble film is a continuous dissolving film similar to Examples 1 to 8. There is. However, a combination with slow-dissolving films is of course also possible.

Example 33 contains 1.0 parts by weight of flavonoids as active ingredients as shown in Table 4, HPC-840 parts by weight, and HPC-L.
20 parts by weight of PVP and 100 parts by weight of ethanol
This is an example in which an oral mucosal adhesive type anti-halitosis agent was formed by dissolving 0 parts by weight, spreading and drying, and then forming a single-layer film with a thickness of about 20 μm.

Example 34 has chlorpyridinium chloride as the active ingredient;
No. 35 contains chlorhexidine chloride, No. 36 contains dequalinium chloride, and No. 37 contains chlorhexidine gluconate, and the manufacturing method is the same as above.

(Examples 38 to 42) Table 5 shows examples in which an active ingredient below λ-menthol, which has a taste-correcting and odor-correcting effect, and an active ingredient below flavonoid, which has a deodorizing effect, are used together. Water-soluble film is Example 33
Although a rapid dissolving film is used in the same way as in 31, this can also be combined with a slow dissolving film.

Example 38 is an example in which flavonoid menthol and peppermint oil were used as active ingredients, and Example 39 and below are examples in which the anti-halitosis agent according to the present invention was formed by containing each active ingredient as shown in Table 5. It can be manufactured by the same manufacturing method as above.

The mutual combinations of Examples 1 to 8, Examples 9 to 16, and Examples 33 to 31 were carried out in the same manner as Examples 38 to 42, and almost all of them were examined, and generally good results were obtained. .

[Brief explanation of the drawing]

The drawings relate to the breath odor preventive agent with mucosa attached to the oral cavity according to the present invention, and FIGS. 1 to 5 are enlarged cross-sectional views without showing the cross-sectional structure, and FIG. 6 is a graph showing the halitosis preventing effect of the present invention. It is. Patent application Person: Kyuu Yakuhin Kogyo Co., Ltd. Table 3 Table 5 Recruitment services Figure 2 Figure 3

Claims (12)

[Claims] (1) An oral mucosa patch-type anti-halitosis agent containing an active ingredient having an anti-halitosis effect and consisting of a water-soluble film that adheres to the oral mucosa. (2) Active ingredients include l-menthol, dl-camphor, peppermint oil, fennel oil, acaenia, licorice, chlorophyllin derivatives, cinnamon bark, pepper, shukusha,
Claim 1 containing one or more selected from ginger, clove, chili pepper, dl-menthol, hyakusou, mokko, yakuchi, rhyuno, nikuzuku, clove oil, cinnamon bark oil, saffron, rose oil, and matcha.
The oral mucosal patch type anti-halitosis agent described in 2. (3) The content ratio of each active ingredient is 0.1 to 5% by weight
The oral mucosa patch type halitosis preventive agent according to claim 2. (4) Oral mucosa adhesive type halitosis according to claim 1 or 2, which contains one or more selected from flavonoids, cetylpyridinium chloride, chlorhexidine chloride, dequalinium chloride, and chlorhexidine gluconate as active ingredients. Inhibitor. (5) The content ratio of each active ingredient is 0.01 to 5 by weight.
% of the oral mucosa patch type halitosis preventive agent according to claim 4. (6) The oral mucosa-type anti-halitosis agent according to claim 1, which contains a preservative, an artificial sweetener, and other food additives in addition to the active ingredient. (7) The water-soluble film is one type selected from polyvinylpyrrolidone, gelatin, polyvinyl alcohol, sodium polyacrylate, carboxymethylcellulose, starch, xanthan gum, karaya gum, sodium alginate, methylcellulose, carboxyvinyl polymer, agar, and hydroxypropylcellulose. or the oral mucosa patch type halitosis preventive agent according to claim 1, which contains two or more types as main ingredients. (8) The oral mucosa-type anti-halitosis agent according to claim 1, wherein the water-soluble film is a single-layer film. (9) The oral mucosa-type anti-halitosis agent according to claim 1, wherein the water-soluble film is a multilayer film. (10) The oral mucosa-type anti-halitosis agent according to claim 1, wherein the water-soluble film is a laminated film having three or more layers. (11) The oral mucosal adhesive type anti-halitosis agent according to claim 8, 9, or 10, wherein at least one layer of the water-soluble film is a slow-dissolving film that lasts longer than the other layers. (12) The agent thickness, that is, the thickness of the water-soluble film is 15 to 330
The oral mucosal adhesive type anti-halitosis agent according to claim 1, which has a particle size of .mu.m.