JPH0513131B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to a breath odor remover, and more specifically,
The present invention relates to a halitosis remover applied to the oral mucosa, which easily adheres to the oral mucosa for a long time, and the elution of the anti-halitosis agent into saliva lasts for a long time, thereby efficiently removing bad breath. (Relationship with Prior Art) In general, bad breath is broadly classified into three types depending on the cause: bad breath caused by the oral cavity, bad breath caused by diseases of internal organs other than the oral cavity, and bad breath caused by food and drink. These bad breaths have become an important problem in today's life where there are many social occasions, such as causing mental pain to the person and/or discomfort to others, and effective measures against bad breath are desired. . Conventionally, efforts to eliminate bad breath have been made on toothpastes, mouthwashes, liquid preparations, pills, chewing gums, candies, jellies, and the like. However, all of these have a short duration of effectiveness, and furthermore, products that are kept in the mouth for a certain period of time and chewed or licked have the disadvantage that they can cause problems in interpersonal relationships. are doing. (Object of the Invention) In view of the above-mentioned drawbacks of conventional products for removing bad breath, the object of the present invention is to adhere to the oral mucosa, not to peel off during normal activities such as eating, drinking, and talking, and to eliminate the sensation of a foreign body. Instead, the object is to provide a new type of oral mucosa-applicable halitosis remover in which the elution of the halitosis preventive agent into saliva continues for a long period of time. (Description of the Structure of the Invention) As a result of intensive efforts to obtain the above-mentioned product, the present inventors have discovered a product having a layer consisting of a specific component that gradually dissolves an anti-halitosis agent, and in particular a product that has a layer consisting of a specific component that gradually dissolves an anti-halitosis agent. It has been found that this object is achieved with a product consisting of at least two layers: a moderately retarding layer (I) and a highly retarding layer (). That is, the present invention provides a halitosis remover for oral mucosa, comprising at least two layers: layer (I) and layer () below, and containing an anti-halitosis agent in layer (I) and layer (). be. Layer (I): one or more polymer components selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and its pharmaceutically acceptable salts, and alternating copolymers of maleic anhydride and methyl vinyl ether. The polymer component is an essential component, with excipients and other additives added as necessary, and the polymer component is at least 20% by weight based on the total composition of layer (I).
The layer that is. Layer (): one or more polymer components (A ) and one or more polymer components (B) selected from the group consisting of polyacrylic acid and its pharmaceutically acceptable salts, and excipients and other additives as necessary. Additionally, a layer in which the weight ratio of polymer component (A) and polymer component (B) is 70:30 to 95:5. Next, the present invention will be explained in detail. Layer (I) comprises one or more polymer components selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and its pharmaceutically acceptable salts, alternating copolymers of maleic anhydride and methyl vinyl ether, and One or more anti-halitosis agents are an essential component, and the action of moderately retarding the release of the anti-halitosis agents is brought about by the polymer component. In addition to the above-mentioned polymer components and anti-halitosis agents, this layer can contain excipients and other additives as necessary. The polymer component is 20% by weight of the total composition in layer (I)
Preferably it is 50% by weight. This is because when the amount of the polymer component is less than 20% by weight, the elution of the anti-halitosis agent is too fast and the elution cannot be sustained for a long time even when combined with a layer that highly retards elution, and when the amount of the polymer component exceeds 50% by weight. This is because the layer cannot serve as a layer that moderately delays elution because of the delayed elution. On the other hand, the layer () contains one or more polymer components A selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alginic acid, and its pharmaceutically acceptable salts, and polyacrylic acid and its pharmaceutically acceptable salts. three components (A), (B), and (C) of one or more polymer components (B) selected from the group consisting of salts such as is an essential component, and the effect of highly delaying the release of the anti-halitosis agent is brought about by the combination of the polymer component (A) and the polymer component (B). Polymer component (A) alone does not have a sufficient release retardation effect, and component (B) alone exhibits a sufficient release retardation effect, but the swelling property is too strong, giving a strong foreign body sensation. From this point of view, the weight ratio of polymer component (A) and polymer component (B) is 70:30 ~
The ratio must be 95:5. In addition, excipients and other additives can be added to the () layer as necessary, but in order to fully demonstrate the effect, additions other than (A), (B), and (C) are required. It is preferable that the amount of substances such as excipients and other additives is 20% by weight or less of the total composition in layer (2). Furthermore, the layer () has strong adhesion to the oral mucosa due to the presence of both the adhesive polymer components (A) and (B). The polymer components used in the above () and () layers, polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and its pharmaceutically acceptable salts,
Alternating copolymers of maleic anhydride and methyl vinyl ether can be used as long as they do not affect their physicochemical properties.
This also includes copolymers of two or more elements with one or more other monomers, and crosslinked polymers crosslinked with a suitable crosslinking agent. In order not to affect the physicochemical properties, it is desirable that the copolymerization ratio of other monomers is 30 mol% or less. The pharmaceutically acceptable salts herein include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts, ammonium salts, and the like. In the case of other polymer components used in the () layer, polyacrylic acid and its pharmaceutically acceptable salts, each may be a homopolymer, a copolymer of two or more elements with one or more other monomers, or a suitable This includes crosslinked polymers crosslinked with a crosslinking agent and does not affect the physicochemical properties of the homopolymer.
In the case of a copolymer, it is preferred that other monomers are copolymerized in an amount of 30 mol% or less. Commercially available products such as Carbopol 934, Carbopol 940, and Carbopol 941 can be used as suitable examples. In the present invention, anti-halitosis agents include substances that act on bad breath compounds such as sodium copper chlorophyllin, lecithin, green tea flavonoids, vitamin C, and carbonized plant ingredients, and as necessary, oral disinfectants, antibacterial agents, and anti-inflammatory agents. Agents, plaque inhibitors, deodorants, etc. can be added. The anti-halitosis agent is present in an amount of 0.05 to 20% by weight, preferably 0.1 to 10% by weight, based on the total composition of layer (I) and layer (). In the present invention, excipients include starch, crystalline cellulose, dextrin, lactose, mannitol, sorbitol, anhydrous calcium phosphate, and the like. In the present invention, other additives include lubricants, binders, flavoring agents, and the like. As a lubricant,
Examples include talc, stearic acid and its salts, waxes, etc. Binding agents include starch, dextrin, tragacanth, gelatin, hydroxypropylcellulose, etc., and flavoring agents include citric acid, fumaric acid, Examples include tartaric acid, menthol, citrus flavor, and the like. In layer (I), excipients, anti-halitosis agents and other additives are preferably present in an amount of 80 to 50% by weight based on the total composition. The oral mucosa-applicable halitosis remover provided by the present invention can be prepared using a breath freshener selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and its pharmaceutically acceptable salts, and alternating copolymers of maleic anhydride and methyl vinyl ether. Type 1 or 2
one or more polymer components, one or more anti-halitosis agents, and, if necessary, one of excipients, lubricants, binders, flavoring agents, and coloring agents to improve appearance or odor. A method in which the seeds or two or more seeds are thoroughly mixed to form a homogeneous mixture, and an appropriate amount of these is directly pressurized using a punch, die, or press, or pressurized through an appropriate granulation process. After molding the (I) layer by a molding method, polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and a pharmaceutically acceptable salt thereof,
one or more polymer components (A) selected from the group consisting of alternating copolymers of maleic anhydride and methyl vinyl ether; and one or more polymer components selected from the group consisting of polyacrylic acid and pharmaceutically acceptable salts thereof. one or more polymer components (B) and one or more anti-halitosis agents (C), as well as excipients, lubricants, binders, flavoring agents, and coloring agents as necessary. No. 1
It can be easily produced by placing a species or a mixture of two or more species uniformly on the layer (I) and applying further application. Another method for producing the oral mucosa-applicable halitosis remover provided by the present invention is to separately dissolve the components constituting the layers (I) and () in a suitable solvent, and then
Two layers are formed by casting, drying, forming into a thin film, and bonding with a suitable adhesive, moistening with water or other solvent and pressing, or pressing using heat. You can get the lock. The ratio of the thickness of layer (I) and layer () is 1:9 to 9:1,
Preferably it is 3:7 to 7:3. The oral mucosa-applicable halitosis remover of the present invention has a layer ().
In addition to the two-layer structure of and layer ( ), it may have a structure of three or more layers. Application of the product of the present invention is not particularly limited, and the () layer side is applied to the gums and inner cheek mucosa. The () layer side of the product of the present invention also has adhesive properties to mucous membranes due to the presence of the adhesive polymer, but when this is applied, for example, to the outside of the gums with the () layer side adhered, the () layer side adheres to the buccal mucosa. There may be some adhesion, but this is not a problem. (Effects of the Invention) As described above, the present invention provides a halitosis remover applied to the oral mucosa having a layer that gradually releases an anti-halitosis agent, particularly a layer (I) that moderately delays the release of an anti-halitosis agent, and a layer (I) that gradually delays the release of an anti-halitosis agent. At least 2 of the layers () delayed to
It is a halitosis remover that can be applied to the oral mucosa and consists of a layer that releases the anti-halitosis agent over a long period of time, easily adheres to the oral mucosa, does not come off easily during normal activities such as eating, drinking, and talking, and has no odor at all. This is a new type of breath odor remover that does not feel like a foreign body. The most important feature of the product of the present invention is that the elution rate of the anti-halitosis agent into saliva is sustained over a long period of time, and it is expected that the effectiveness of the anti-halitosis agent in removing bad breath can be greatly improved. . The second feature of the product of the present invention is that it easily adheres to the oral mucosa, and its adhesiveness lasts for 4 to 24 hours.
It is about sustaining. Moreover, this adhesiveness is due to drinking,
It is not affected by daily oral movements such as smoking, drinking coffee, eating, and talking, and does not cause problems in interpersonal relationships unlike chewing gum or candy. The third feature of the product of the present invention is that the molded product swells with saliva in the mouth and becomes extremely soft, so there is almost no foreign body sensation. A fourth feature of the product of the present invention is that the adhesion and persistence can be adjusted by changing the composition of the layer (I) that moderately retards the elution of the anti-halitosis agent and the layer that retards the elution of the halitosis agent highly. The advantage is that it can be carried out as desired, and that the optimal elution performance depending on the action of the halitosis preventive agent can be obtained as desired by adjusting the ratio of the amounts of layer (I) and layer (). (Examples) Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited thereto. In the examples, parts or % simply indicate parts by weight or % by weight. Test method 1 Panel test The product of the present invention was applied to 9 subjects, and after a predetermined period of time, 5 experienced inspectors inspected the presence or absence of bad breath. The evaluation was divided into four levels: no halitosis removal effect (-), some effect (+), some effect (), and significant effect (2). Test method 2 Measurement of bad breath substances in oral gas The product of the present invention was applied to a group of 3 subjects, and 5 ml of oral gas was collected using a gastight syringe before and after the application, and analyzed using gas chromatography. The concentration of methyl mercaptan, which is one of the substances that cause bad breath, was measured, and its deodorization rate was determined. Deodorization rate (%) = CH ₃ SH concentration before application - CH ₃ SH after application
Concentration / CH ₃ SH concentration before application x 100 Example 1 (I) layer Polyvinylpyrrolidone (molecular weight 40,000) 28.24% d-mannitol 65.90% Chlorhexidine hydrochloride 2.86% Green tea flavonoids 0.99% - Menthol 0.86% Vanilla powder 1.14% Food red 3 No. 0.002% After uniformly mixing the above composition, tableting it, (I)
formed a layer. () layer Polyacrylic acid 6.63% Polyvinylpyrrolidone (molecular weight 360,000) 87.24% Chlorhexidine hydrochloride 4.29% Flavonoid 0.98% Vanilla powder 0.86% After uniformly mixing the above () layer composition, place it on the above (I) layer, Compressed tablet weighs 70mg, thickness
A track field type two-layer tablet with a length of 1.75 mm, a major axis of 8.8 mm, and a minor axis of 4.4 mm was obtained. The obtained product was examined for its effectiveness in removing bad breath through a panel test. The results are shown in Table 1.
In addition, when the obtained product was applied to a subject, the amount of bad breath substances in the oral gas was measured. The results are shown by -○- in FIG. Example 2 () layer Polyvinylpyrrolidone (molecular weight 40,000) 28.22% d-mannitol 62.60% Copper chlorophyllin sodium 8.57% Flavonoid 0.89% - Menthol 0.86% Vanilla powder 2.86% () layer Polyacrylic acid 6.94% Polyvinylpyrrolidone (molecular weight 36) 91.18% Flavonoids 1.02% Vanilla powder 0.86% Two-layer tablets similar to those in Example 1 were obtained. The obtained product was examined for its effectiveness in removing bad breath through a panel test. The results are shown in Table 1.
Further, in the same manner as in Example 1, substances with bad breath were measured. The results are shown by -●- in FIG. Example 3 () Layer Polyvinylpyrrolidone (molecular weight 40,000) 28.46% d-Mannitol 66.39% Chlorhexidine hydrochloride 2.86% Lecithin 0.29% - Menthol 0.86% Vanilla powder 1.14% Food Red No. 3 0.002% () Layer Polyacrylic acid 6.60% Polyvinyl Pyrrolidone (molecular weight: 360,000) 87.54% Chlorhexidine hydrochloride 4.29% Lecithin 0.71% Vanilla powder 0.86% Two-layer tablets similar to those in Example 1 were obtained. The obtained product was examined for its effectiveness in removing bad breath through a panel test. The results are shown in Table 1.
Further, in the same manner as in Example 1, substances with bad breath were measured. The results are shown by -◎- in Fig. 1.

[Table] From Table 1, it can be seen that the halitosis removing agent for oral mucosa of the present invention is extremely effective in removing bad breath. Comparative Example 1 Single-layer tablet consisting only of layer (I) of the present invention Polyvinylpyrrolidone (molecular weight 40,000) 36.9% d-mannitol 55.4% Sodium copper chlorophyllin 4.3% Green tea flavonoids 1.0% - Menthol 0.4% Vanilla powder 2.0% Above composition After mixing uniformly, tablet it to a weight of 70.
A track field type single-layer tablet with a thickness of 1.75 mm, a major axis of 8.8 mm, and a minor axis of 4.4 mm was obtained. When this tablet was applied to a subject, the amount of bad breath substances in the oral gas was measured according to Test Method 2. The results are shown by -○- in FIG. Comparative Example 2 Single-layer tablet consisting of only layer () of the present invention Polyvinylpyrrolidone (molecular weight 360,000) 65.6% Polyacrylic acid 28% Sodium copper chlorophyllin 3.0% Flavonoid 1.0% - Menthol 0.4% Vanilla powder 2.0% The above composition was uniform Comparative Example 1
A single-layer tablet similar to that was obtained. When this tablet was applied to a subject, the amount of bad breath substances in the oral gas was measured according to Test Method 2. The results are shown by -●- in FIG. From FIG. 1 and FIG. 2, it can be seen that the oral mucosa-applicable halitosis remover of the present invention has a remarkable halitosis-removing effect and lasts for a long time. Example 4 A two-layer tablet having the following composition was obtained in the same manner as in Example 1. (I) Layer Polyvinyl alcohol 30.8% d-Mannitol 61% Sodium copper chlorophyllin 5% Green tea flavonoids 1.2% - Menthol 0.86% Vanilla powder 1.14% () Layer Polyvinyl alcohol 83.64% Polyacrylic acid 9.3% Sodium copper chlorophyllin 5% Green tea Flavonoids: 1.2% Vanilla powder: 0.86% The resulting product was applied to subjects, and the amount of bad breath substances in the oral gas was measured. The results are shown by -○- in Fig. 3. Example 5 A two-layer tablet having the following composition was obtained in the same manner as in Example 1. () layer Sodium alginate 41% d-mannitol 50.5% Sodium copper chlorophyllin 6.0% Lecithin 0.5% - Menthol 0.86% Vanilla powder 1.14% () layer Sodium alginate 80.2% Polyacrylic acid 14.16% Sodium copper chlorophyllin 4.0% Lecithin 0.5% Vanilla powder 1.14% The resulting product was subjected to measurement of bad breath substances in the same manner as in Example 4. The results are shown by -●- in Fig. 3. Example 6 A two-layer tablet having the following composition was obtained in the same manner as in Example 1. () layer Maleic anhydride-methyl vinyl ether alternating copolymer 18% d-mannitol 72% Green tea flavonoids 1% Chlorhexidine hydrochloride 7% Vanilla powder 1.14% - Menthol 0.86% Food Red No. 3 0.002% () layer Maleic anhydride-methyl Vinyl ether alternating copolymer 85.8% Polyacrylic acid 4.56% Green tea flavonoid 1.5% Chlorhexidine hydrochloride 7% Vanilla powder 1.14% The obtained product was subjected to measurement of bad breath substances in the same manner as in Example 4. The results are shown by -◎- in Fig. 3. Example 7 A two-layer tablet having the following composition was obtained in the same manner as in Example 1. (I) layer Polyvinylpyrrolidone (molecular weight 40,000) 38% d-mannitol 57.5% Green tea flavonoids 0.5% Sodium copper chlorophyllin 2.0% -Menthol 0.86% Vanilla powder 1.14% () layer Polyvinyl alcohol 89.44% Polyacrylic acid 4.7% Copper chlorophyllin Filin sodium 4.0% Green tea flavonoids 1.0% Vanilla powder 0.86% The resulting product was subjected to the measurement of bad breath substances in the same manner as in Example 4. The results are shown by -ⓓ- in Fig. 3.

[Brief explanation of the drawing]

FIGS. 1 and 3 show changes over time in the deodorization rate of bad breath substances in oral gas when the product of the present invention was applied to subjects. FIG. 2 shows the time change in the deodorization rate of bad breath substances in the oral gas when the comparative product was applied to subjects.

Claims (1)

[Claims] 1. At least two of the following layer (I) and layer ()
1. A halitosis remover for oral mucosa, comprising layers, and layer (I) and layer () containing an anti-halitosis agent. Layer (I): one or more polymer components selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, alginic acid and its pharmaceutically acceptable salts, and alternating copolymers of maleic anhydride and methyl vinyl ether. The polymer component is an essential component, with excipients and other additives added as necessary, and the polymer component is at least 20% by weight based on the total composition of layer (I).
The layer that is. Layer (): one or more polymer components (A ) and one or more polymer components (B) selected from the group consisting of polyacrylic acid and a pharmaceutically acceptable salt thereof, as an essential component,
A layer in which excipients and other additives are added as necessary, and the weight ratio of polymer component (A) to polymer component (B) is 70:30 to 95:5.