Mouthpiece

Abstract

To provide a mouthpiece being worn on a tooth row for a long time without adversely affecting teeth or gums and capable of improving dental caries, periodontal disease, oral infections caused by fungus, etc.SOLUTION: A mouthpiece used with it worn on the tooth row of a human or mammal, the mouthpiece can cover a part or whole of the tooth row, and a part of gums on an oral vestibule side continuing from the part or whole of the tooth row, and contains surface-modified zinc oxide. Alternatively, a mouthpiece used with it worn on the tooth row of a human or mammal, the mouthpiece includes a first layer in contact with the tooth row, and a second layer on the surface of the first layer, opposite to the side in contact with the tooth row, and one or both of the first layer and the second layer contain surface-modified zinc oxide.SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] The present invention relates to a mouthpiece, and in particular to a mouthpiece having antibacterial properties. [Background technology]

[0002] It has been revealed that dental caries and periodontal disease, the two major diseases in the dental field, are both caused by oral resident bacteria. In other words, plaque bacteria, which are composed of oral resident bacteria such as Streptococcus mutans and their metabolic products, are the direct cause of dental caries induction, while the proliferation of obligate anaerobic gram-negative bacteria such as Porphyromonas gingivalis in the subgingival area causes gingival inflammation and periodontal tissue destruction. Therefore, it is clear that inhibiting the proliferation of bacteria that compose plaque is important for preventing these diseases.

[0003] Denture stomatitis is an inflammation of the mucosa beneath removable dentures and orthodontic appliances, and is closely related to oral microorganisms. It has been reported that denture plaque, which is mainly composed of fungi such as Candida albicans found on the mucosal surface of the denture base, is an important factor in denture stomatitis. It has been reported that the main bacteria that make up denture plaque are facultative anaerobic gram-positive cocci and facultative anaerobic gram-positive rods. It has also been reported that there is a correlation between denture stomatitis and Candida and Staphylococcus, and that Candida species, mainly Candida albicans, are frequently detected in denture plaque.

[0004] Mouthpieces are also used for the treatment of stomatitis caused by other diseases, temporomandibular joint disorders, and clenching, as well as for orthodontic purposes. Depending on the purpose of use, mouthpieces may be worn even while sleeping, and since they are in close contact with the dentition for long periods of time, an environment may be created that is conducive to the proliferation of not only bacteria that cause dental caries and periodontal disease, but also various types of bacteria and fungi.

[0005] In particular, when bacteria that cause dental caries, bacteria that cause periodontal disease, and other pathogenic bacteria and fungi are present in the oral cavity, these bacteria are particularly likely to proliferate around mouthpieces made of resin, which can damage healthy teeth around the dentures and cause stomatitis, etc. In addition, periodontal disease patients often have a strong bad breath caused by methyl mercaptan and other substances produced by periodontal disease-causing bacteria.

[0006] In order to improve the above situation, Patent Document 1 discloses dentures and a mouthpiece (night guard) in which surface-modified zinc oxide is contained in an acrylic resin as an antibacterial component.

[0007] Patent Document 2 discloses a mouthpiece having a two-layer structure with an inner layer facing the dentition and an outer layer formed on the outer side thereof, in which the resin constituting the outer layer contains polyphenol, and the polyphenol tannin is continuously released into the oral cavity, thereby treating and preventing oral fungal infections. Patent Document 2 also discloses that the mouthpiece is preferably formed so that the gums are exposed.

[0008] Patent Document 3 discloses a mouthpiece with a two-layer structure consisting of a hard part (outside) and a soft part (inside) used for the purpose of treating obstructive sleep apnea syndrome. The soft part of this mouthpiece uses a polymer gel that can improve the fit of the mouthpiece and can be restored to the same state as before it was broken by biting down. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] JP 2022-190418 A [Patent Document 2] Patent No. 7016137 [Patent Document 3] Patent Publication No. 2022-099808 Summary of the Invention [Problem to be solved by the invention]

[0010] The object of the present invention is to provide a mouthpiece that, even when worn on the dentition for long periods of time, does not adversely affect the teeth or gums, does not worsen dental caries, periodontal disease, fungal oral infections, etc., and can even improve or treat such conditions. [Means for solving the problem]

[0011] According to the present invention, the following mouthpiece etc. are provided. 1. A mouthpiece for use by attaching it to the dentition of a human or mammal, It can cover a part or all of the dentition and a part of the gingiva on the oral vestibule side continuing from the part or all of the dentition, A mouthpiece containing surface-modified zinc oxide. 2. A mouthpiece for use by attaching it to the dentition of a human or mammal, a first layer in contact with the dentition; and a second layer on a surface opposite to a surface of the first layer that contacts the row of teeth; A mouthpiece, wherein one or both of the first and second layers contain surface-modified zinc oxide. 3. The mouthpiece according to 1 or 2, wherein the zinc oxide powder has an average particle size in the range of 1 to 500 nm. 4. The mouthpiece described in 1 or 2, wherein the surface modification is coating with a zinc sulfide film. 5. The mouthpiece described in 1 or 2, wherein the surface modification is coating with a coupling agent. 6. The mouthpiece described in 1 or 2, wherein the surface modification is a partial coating of the zinc oxide powder surface. 7. The mouthpiece according to 1 or 2, wherein the coating amount of the zinc sulfide or coupling agent is 0.1 to 30% by mass. 8. The mouthpiece according to 1 or 2, wherein the blending amount of the surface-modified zinc oxide powder is 0.1 to 10 mass %. 9. A mouthpiece described in 1 or 2, which inhibits the growth of periodontal disease-causing bacteria, caries-causing bacteria and / or fungi. 10. A mouthpiece described in 1 or 2, which suppresses the adhesion of denture plaque. 11. A mouthpiece as described in 1 or 2, which reduces substances that cause bad breath. 12. A mouthpiece described in 1 or 2, which is for the treatment or prevention of peri-implantitis. 13. A mouthpiece described in 1 or 2, which is used either before or after installation of an implant, or both. 14. The mouthpiece of claim 1, which is made of a material having rubber elasticity. 15. The mouthpiece described in 1, wherein the material having rubber elasticity includes one or more selected from the group consisting of ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU). 16. The mouthpiece according to 2, wherein the material constituting the first layer is different from the material constituting the second layer. 17. The mouthpiece described in 2, wherein the first layer is made of a material having rubber elasticity. 18. The mouthpiece described in 2, wherein the first layer is composed of a material including one or more selected from the group consisting of ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU). 19. The mouthpiece described in 2, wherein the second layer is made of a material having a higher rigidity than the material constituting the first layer. 20. The mouthpiece described in 2, wherein the second layer is composed of a material including one or more selected from the group consisting of polyethylene terephthalate (PET) and polyethylene terephthalate glycol (PETG). 21. The mouthpiece described in 2, wherein the first layer, or the first layer and the second layer, cover part or all of the dentition and part of the gingiva on the vestibular side of the oral cavity continuing from part or all of the dentition. 22. A mouthpiece according to 1 or 2, and A topical agent containing an antibacterial agent against periodontal disease-causing bacteria A kit for treating periodontal disease or peri-implantitis comprising: 23. The kit for treating periodontal disease or peri-implantitis according to 22, wherein the drug is henbit or an extract thereof. Effect of the Invention

[0012] According to the present invention, a mouthpiece can be provided that, even when worn on the dentition for long periods of time, does not adversely affect the teeth or gums, does not worsen dental caries, periodontal disease, fungal oral infections, etc., and can even improve or treat such conditions. [Brief description of the drawings]

[0013] [Figure 1A] 1 is a photograph showing a state in which a mouthpiece of a first embodiment, which covers up to a part of the gums on the vestibule side of the oral cavity, is attached to a dental model. [Figure 1B] 1B is a photograph of the first embodiment of the mouthpiece of FIG. 1A from another angle. [Figure 2A] 1 is a photograph showing a conventional mouthpiece made of PET resin that does not cover the gums on the vestibular side of the oral cavity, attached to a dental cast. [Figure 2B] 1 is a photograph showing a conventional mouthpiece made of EVA resin that does not cover the gums on the vestibular side of the oral cavity, attached to a dental model. [Diagram 3] 1 is a photograph showing a state in which a mouthpiece of a second embodiment is attached to a dental model. [Figure 4A] 1 is a photograph of a first embodiment of a mouthpiece that contains surface-modified zinc oxide used in a test example and covers up to a portion of the gums. [Figure 4B] 1 is a photograph of a mouthpiece (comparative example) that does not contain the surface-modified zinc oxide used in the test examples and covers part of the gums. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] 1. Mouthpiece of the First Aspect The mouthpiece according to the first aspect of the present invention comprises: A mouthpiece for use by being attached to the dentition of a human or mammal, It can cover a part or all of the dentition and a part of the gingiva on the oral vestibule side continuing from the part or all of the dentition, It is characterized by containing surface-modified zinc oxide.

[0015] The term "mouthpiece" as used in the present invention refers to a device used in the treatment of diseases in dentistry or oral surgery, for orthodontics, or as a sports tool, and is worn to cover a part or the whole of the dentition. There are mouthpieces for medical use, such as night guards and splints, and mouthpieces for sports, but the term "mouthpiece" as used in the present invention is a concept that includes all of these. Night guards are used to prevent teeth grinding and clenching during sleep, which can lead to tooth wear, cracking due to strong pressure on the teeth, and the progression of periodontal disease. They are also used to treat sleep apnea syndrome. Splints are intended to relieve symptoms of temporomandibular joint disorder and can relieve tension in the muscles used when eating (chewing muscles) and jaw joint.

[0016] The mouthpiece of the first embodiment has a structure that covers a part or all of the dentition and a part of the gingiva on the oral vestibule side that continues from the part or all of the dentition. The "oral vestibule" refers to the gingiva on the lip side of the dentition. Conventional mouthpieces are formed so as not to cover the gums, as shown in Figures 2A and 2B. This is because covering the gums, including the periodontal pockets, creates an environment that is favorable for the proliferation of obligate anaerobic bacteria that cause periodontal disease, which can worsen periodontal disease and dental caries. Furthermore, covering the gums makes it difficult to put on and take off due to undercuts formed by the dentition and tooth shape. In contrast, the mouthpiece of this embodiment is formed to cover a part of the gingiva on the oral vestibule side continuing from a part or all of the dentition, as shown in Figures 1A and 1B. The mouthpiece of the present invention contains surface-modified zinc oxide, which will be described later, in its material, and therefore does not worsen caries or periodontal disease even when it covers the gingiva including the periodontal pocket, but rather has the effect of improving periodontal disease.

[0017] Here, "all of the dentition" means that the mouthpiece covers the entire maxillary dentition, the entire mandibular dentition, or the entire maxillary and mandibular dentitions. "Part of the dentition" means that the mouthpiece covers only a part of the dentition, for example, only the front teeth or only the molars. Also, for example, a case where the mouthpiece does not cover the entire dentition but a part of the occlusal surface is cut (removed) is also included in the case of covering "part of the dentition."

[0018] The shape of the mouthpiece of the first embodiment to cover up to what position on the gingiva on the vestibular side of the oral cavity (the length of the base edge) should be appropriately selected depending on the purpose of use of the mouthpiece, the condition of the attachment part, the shape of the patient's dentition and gingiva, etc., but the upper limit position is preferably up to a position that does not interfere with the upper or lower labial frenulum. The length of the base edge of the mouthpiece of the first embodiment is preferably such that the wearer does not feel uncomfortable when wearing the mouthpiece and is effective, and also depends on the wearer's preference.

[0019] For example, when used as a night guard for patients with periodontal disease, the length of the base edge is preferably set to be such that it can cover the periodontal pocket. More specifically, to cover the periodontal pocket, it is preferable to cover up to about 2 mm from the gum end of the dentition, more preferably up to about 3 mm, and even more preferably up to about 5 mm.

[0020] The mouthpiece of the first embodiment, which can cover up to a part of the gums, may have a shape in which a part of the occlusal surface is cut (removed). In other words, instead of covering the entire dentition, a part of the occlusal surface of the dentition may be removed and the occlusal surface of the dentition in that part may be exposed (not covered by the mouthpiece). With the shape of the mouthpiece of the first embodiment, even if a part of the occlusal surface of the dentition is exposed, the base edge of the mouthpiece covers up to a part of the gums, so that the mouthpiece can be held by the undercut of the entire dentition part covered by the mouthpiece, and the mouthpiece will not fall off. The advantages of the above-mentioned mouthpiece with a part of the occlusal surface cut out include the reduction of discomfort on the occlusal surface, the reduction of strain on the temporomandibular joint, etc. Also, while a mouthpiece that covers the entire occlusal surface cannot be worn while eating, a mouthpiece with a part of the occlusal surface cut out has the advantage that it is possible to eat while wearing the mouthpiece.

[0021] The mouthpiece of the first embodiment can be made of a resin material that has been used as a material for mouthpieces in the past. For example, polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (EVA), thermoplastic polyurethane (TPU), polyethylene terephthalate glycol (PETG), etc. Also, it can be made of various resins (composite resins) used in the dental field.

[0022] The mouthpiece of the first aspect is preferably made of a material having rubber elasticity. Because the mouthpiece is made of a material with rubber elasticity, it has cushioning properties, which reduces the strain on the teeth and gums and the discomfort caused by tight contact, and is easy to put on and take off even when it covers the gums.

[0023] The rubber-elastic material that constitutes the mouthpiece may be any material that is easy to mix uniformly with the surface-modified zinc oxide that is to be blended therein, such as ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU). Among these, ethylene-vinyl acetate copolymer (EVA) is preferable.

[0024] The average thickness of the mouthpiece of the first embodiment should be appropriately selected depending on the purpose, but for medical use, it is generally 5.0 mm or less, preferably 2.0 mm or less, more preferably 1.5 mm or less. The average thickness of the mouthpiece is generally 0.5 mm or more, preferably 1.0 mm or more. The thickness of the mouthpiece is shown as an average thickness since there may be some variation depending on the part. If the average thickness of the mouthpiece exceeds 5.0 mm, it may be difficult to close the mouth by fitting the upper and lower teeth together, and if it is less than 0.5 mm, it may not be strong enough and may be prone to breaking during use.

[0025] 2. Mouthpiece of the Second Embodiment The mouthpiece according to the second aspect of the present invention comprises: A mouthpiece for use by being attached to the dentition of a human or mammal, a first layer in contact with the dentition; and a second layer on a surface opposite to a surface of the first layer that contacts the row of teeth; One or both of the first and second layers are characterized in that they contain surface-modified zinc oxide.

[0026] The mouthpiece of the second embodiment has a multi-layer structure having a first layer (hereinafter sometimes referred to as the "inner layer") that contacts the dentition, and a second layer (hereinafter sometimes referred to as the "outer layer") formed on the side of the first layer opposite the side that contacts the dentition. The multi-layer structure is not limited to two layers, a first layer (inner layer) and a second layer (outer layer), but may, for example, have a third layer (middle layer) between the first layer (inner layer) and the second layer (outer layer). The third layer (intermediate layer) may be a layer having a function of bonding the first layer and the second layer.

[0027] The first layer, the second layer, and the third layer can be formed from the resin material previously used as a mouthpiece material, as described in the first embodiment of the mouthpiece.

[0028] By making the mouthpiece into a multi-layer structure, for example by layering an inner layer made of a flexible material and an outer layer made of a material with a certain degree of hardness, it is possible to improve the strength of the mouthpiece itself while reducing the burden on the teeth and gums. In other words, a mouthpiece made only of a flexible material is prone to wear and tear at the biting area when used, but by making it into a multi-layer structure, it is possible to improve or enhance the durability of the mouthpiece.

[0029] For the above reasons, it is preferable that the material constituting the first layer is different from the material constituting the second layer. The first layer is preferably made of a material having rubber elasticity. Since the first layer is made of a material having rubber elasticity, it has cushioning properties, and can reduce the burden on the teeth and gums and the discomfort caused by tight contact.

[0030] The material having rubber elasticity to be used for the first layer may be any material that can easily mix uniformly with the surface-modified zinc oxide to be blended therein, such as ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU). Among these, ethylene-vinyl acetate copolymer (EVA) is preferable.

[0031] The mouthpiece of the second embodiment may also cover a part or all of the dentition and a part of the gingiva on the vestibule side of the oral cavity that continues from the part or all of the dentition. Only the first layer of the mouthpiece of the second embodiment may cover a part of the gingiva, or both the first layer and the second layer may cover a part of the gingiva. Even when the mouthpiece of the second embodiment is shaped to cover the gums, the first layer is made of a material having rubber elasticity, so that the mouthpiece is easy to put on and take off.

[0032] The second layer is preferably made of a material having a higher stiffness than the material making up the first layer. When the material of the second layer has high rigidity, wear and damage caused by biting the mouthpiece can be suppressed, and the durability of the mouthpiece can be improved or enhanced.

[0033] Examples of the rigid material constituting the second layer include polyethylene terephthalate (PET) and resins (composite resins) used in the dental field.

[0034] When the first layer is made of an elastic material, the second layer is preferably made of a material containing polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), or the like.

[0035] Preferably, the first layer is constructed from ethylene vinyl acetate (EVA) or thermoplastic polyurethane (TPU) and the second layer is constructed from polyethylene terephthalate glycol (PETG).

[0036] In the mouthpiece of the second embodiment, one or both of the first and second layers contain surface-modified zinc oxide. As described below, surface-modified zinc oxide is safe for the human body when used in the oral cavity, does not dissolve or decompose from the materials that make up the mouthpiece, and does not stain or have any adverse effects on the teeth or gums, so it can be incorporated into both the first layer that comes into contact with the dentition and the second layer that comes into contact with the lips, etc.

[0037] The surface-modified zinc oxide is preferably contained in the first layer, and more preferably in both the first and second layers.

[0038] The mouthpiece of the second embodiment is made of multiple layers, and the average thickness of the multiple layers should be appropriately selected depending on the purpose, but for medical use, it is generally 5.0 mm or less, preferably 2.0 mm or less, more preferably 1.5 mm or less. Also, the average thickness of the multiple layers is generally 0.5 mm or more, preferably 1.0 mm or more.

[0039] From the results of the test examples described below, it was confirmed that the mouthpiece made of a resin containing zinc oxide of the present invention reduces the number of bacteria in the oral cavity, in particular by suppressing gram-negative bacteria, thereby restoring the balance between gram-positive and gram-negative bacteria and helping to maintain a healthy immune system in the oral cavity.

[0040] Furthermore, the mouthpiece of the present invention can be used for the treatment and prevention of peri-implantitis. In one embodiment, the mouthpiece of the present invention is used either before or after implant installation, or both. By using the mouthpiece of the present invention before and / or after implant placement, peri-implantitis after implant placement can be prevented. Furthermore, by using the mouthpiece of the present invention on peri-implantitis that has developed, the peri-implantitis can be improved or treated.

[0041] 3. Surface-modified zinc oxide The surface-modified zinc oxide used in the mouthpieces of the first and second embodiments will now be described. "Zinc oxide" is known as an inorganic antibacterial agent that is safe for the human body and effective against common bacteria. Surface-modified zinc oxide powder, which has been modified on the surface to improve dispersibility in resin, also exhibits antibacterial properties against oral bacteria such as bacteria that cause periodontal disease, bacteria that cause dental caries, and fungi (see Patent Document 1).

[0042] When an organic antibacterial agent is used in a mouthpiece, there is a concern that exposure to saliva, etc. in the oral cavity over a long period of time may cause the decomposition of the organic antibacterial compound, resulting in a decrease in antibacterial properties. In contrast, zinc oxide has the advantage that it does not elute or decompose from the mouthpiece even in the oral cavity, and its antibacterial properties last for a long period of time. Furthermore, mouthpieces made of resin containing zinc oxide have the effect of reducing, for example, methyl mercaptan, a substance that causes strong bad breath in patients with periodontal disease (Patent Document 1).

[0043] The mouthpiece made of the resin containing zinc oxide of the present invention not only exhibits antibacterial properties over a long period of time, even during sleep when saliva secretion is reduced, but also has the function of decomposing substances that cause strong bad breath, such as methyl mercaptan, and suppressing the adhesion of plaque, which is expected to suppress the worsening of periodontal disease and reduce bad breath.

[0044] (Surface modification of zinc oxide) "Surface modification" of zinc oxide powder refers to a process in which the surface of zinc oxide powder is partially coated to suppress the photocatalytic activity of zinc oxide and improve its dispersibility in resin, without impairing its antibacterial properties against bacteria that cause periodontal disease and bacteria and fungi that cause dental caries, and its deodorizing effects against bad breath.

[0045] Examples of the "surface modification" method for zinc oxide powder include the following methods. In this method, zinc oxide powder is brought into contact with hydrogen sulfide or sulfurous acid gas to sulfurize the surface of the zinc oxide powder and coat the surface of the zinc oxide powder with zinc sulfide. Specifically, zinc oxide powder is placed in a glass container, and hydrogen sulfide gas or sulfurous acid gas is passed through the container while the container is vibrated to bring the powder into contact with the zinc oxide powder.

[0046] The surface of the zinc oxide powder is coated with a coupling agent to obtain a coated zinc oxide powder. The coating treatment of the surface of zinc oxide powder with a coupling agent may be performed by any of the following methods: a wet method in which a coupling agent is added while stirring a slurry of zinc oxide powder in water or a non-aqueous solvent; a dry method in which a coupling agent is sprayed or dropped onto the zinc oxide powder while stirring it at high speed using a Henschel mixer or high-speed mixer capable of high-speed rotation; and a gas phase method in which a coupling agent carried by an inert gas such as nitrogen is introduced into a reaction vessel containing zinc oxide powder to perform coating treatment.

[0047] As the coupling agent, a silane coupling agent having a silanol group, an epoxy group, a methacryl group, a vinyl group, a mercapto group, an amino group, etc. In addition, other coupling agents such as titanium-based, aluminum-based, zirconium-based, zircoaluminate-based, or silanes other than the silane coupling agent may be used.

[0048] The average particle size of the zinc oxide powder is preferably in the range of 1 to 500 nm, more preferably 10 to 400 nm, and even more preferably 50 to 300 nm. Within the above range, the dispersibility in the dental resin is not impaired, and the powder can be mixed uniformly.

[0049] The specific surface area of ​​zinc oxide powder by the BET method is 10 to 500 m 2 / g, and 10 to 400m 2 / g is more preferable, and 20 to 300m 2 / g is more preferred.

[0050] In order to partially coat the surface of the zinc oxide powder, the amount of coating with the zinc sulfide film and coupling agent can be adjusted taking into account the specific surface area of ​​the zinc oxide powder, and can be determined appropriately depending on the intended use of the surface-modified zinc oxide powder. In the case of dental resin materials, the coating amount is preferably in the range of 0.1 to 30% by mass, more preferably 0.2 to 20% by mass, and even more preferably 0.2 to 15% by mass. Within the above range, zinc oxide can be easily dispersed uniformly in the resin, the antibacterial properties of zinc oxide against bacteria causing periodontal disease, bacteria causing dental caries, fungi, etc. are not lost, and the decomposition ability of substances causing bad breath, etc. can be maintained.

[0051] An example of a commercially available "surface-modified zinc oxide powder" that can be used in the dental resin material of the present invention is AD-PSJ (manufactured by ADX Co., Ltd.; average particle size 100 to 200 nm).

[0052] Examples of the "resin" that serves as the base material of the mouthpiece in which the surface-modified zinc oxide powder is dispersed are as described above.

[0053] The means for mixing the surface-modified zinc oxide powder with the resin for forming the mouthpiece may be selected from the methods commonly used by those skilled in the art. In the case of a "polymerization type" in which the mouthpiece is formed by polymerizing the resin, for example, in the case of a two-component resin of powder (polymerization initiator) and liquid (polymerizable monomer), the surface-modified zinc oxide powder may be added in advance to the liquid (polymerizable monomer) and mixed with the powder (polymerization initiator), or the surface-modified zinc oxide powder may be added in advance to the powder (polymerization initiator) and mixed with the liquid (polymerizable monomer). The means for molding the resin material containing the surface-modified zinc oxide powder and the means for curing the same may be selected from methods commonly used by those skilled in the art that are suitable for the base material.

[0054] In the case of the "pressure-fitting" type mouthpiece, in which the mouthpiece is molded from a resin plate, for example, the resin material used for the mouthpiece, such as polyethylene terephthalate (PET) or ethylene-vinyl acetate copolymer (EVA), is heated and softened, and then surface-modified zinc oxide powder is added in the desired ratio (concentration), mixed uniformly, and then formed into a plate. The means for molding the resin plate containing the surface-modified zinc oxide powder, the means for molding by pressure welding, and the means for curing the resin plate may be selected from methods commonly used by those skilled in the art.

[0055] Furthermore, there is also a method in which a batch in which the surface-modified zinc oxide powder is premixed with a resin in a desired ratio, or a master batch in which the surface-modified zinc oxide is premixed with a high concentration, is prepared. From a batch containing the surface-modified zinc oxide mixed in the desired ratio, a required amount can be taken and softened to form a mouthpiece. Alternatively, a required amount of surface-modified zinc oxide may be taken from a master batch containing a high concentration of the surface-modified zinc oxide and mixed into a base resin to obtain a desired final concentration, and then the mouthpiece may be molded.

[0056] In recent years, orthodontic mouthpieces have also been manufactured using 3D printers. When manufacturing mouthpieces using a 3D printer, a powdered or pelleted resin material containing surface-modified zinc oxide powder is used as the raw material for 3D printing to produce a mouthpiece of the desired shape.

[0057] The amount of surface-modified zinc oxide powder in the resin material for a mouthpiece varies depending on the resin used and the application, but is usually within the range of 0.1 to 10 mass%, preferably 0.3 to 5 mass%, more preferably 0.5 to 3 mass%, and even more preferably about 1 mass%.

[0058] In addition to the surface-modified zinc oxide powder, various additives may be added to the resin material for mouthpieces and the mouthpieces made therefrom, depending on the purpose and application of the use, as long as the effect of the surface-modified zinc oxide powder is not impaired. Examples of additives include various additives added to dental articles, such as fillers and colorants. In addition, the material constituting the mouthpiece of the present invention may further contain inorganic antibacterial agents other than zinc oxide or organic antibacterial agents.

[0059] The mouthpiece of the first aspect of the present invention can be manufactured by a method commonly used in the industry, in accordance with the method described in the Examples or Test Examples, and in accordance with the resin material used and the intended application.

[0060] The mouthpiece of the present invention is an antibacterial mouthpiece that contains zinc oxide as an antibacterial agent. In the present invention, "antibacterial" encompasses a range of properties from "bactericidal" that kills bacteria to "bacteriostatic" that inhibits bacterial growth, but "bacteriostatic" is preferred. This is because it is preferable to inhibit the growth of periodontal disease-causing bacteria, caries-causing bacteria, fungi, etc., while maintaining the immunity in the oral cavity without killing the normal oral bacteria, thereby restoring the balance of oral bacteria.

[0061] Here, "bacteriostasis" refers to the action of suppressing the growth and proliferation of bacteria. This refers to a state in which bacteria do not grow and a certain number of bacteria continue to survive. Since a moderate bacterial infection creates a good immune environment for the body, maintaining a bacteriostatic state that temporarily stops bacterial growth is important for keeping the skin and mucous membranes healthy.

[0062] The mouthpiece of the present invention has the properties required of a mouthpiece, such as mechanical strength, flexibility, color tone, color stability, low fatigue, protective properties, low irritation (i.e., no allergic reactions), contamination resistance, bubble-free properties (no air bubbles in which bacteria tend to remain), water resistance (no moisture absorption), adjustability (ability to be used with various resin materials, etc.), and usability with a variety of dental devices. Not only is it antibacterial, it can also inhibit the adhesion of plaque and reduce the bad odor of methyl mercaptan and other substances that cause bad breath.

[0063] 4. Manufacturing method of the mouthpiece according to the first embodiment The mouthpiece of the first embodiment is made up of one layer and can be manufactured by a conventional method. In the first embodiment of a mouthpiece manufactured by pressure welding, which is a widely used method of manufacturing a mouthpiece, an impression of the dentition is taken, plaster is poured into the impression to create a dental model, a resin plate (resin sheet) made of a resin material for mouthpieces containing surface-modified zinc oxide is heated and softened in a pressure molding machine, placed over the dental model, pressurized by air pressure and cooled, integrated with the dental model, excess parts are cut off, the mouthpiece is removed from the dental model, and the cut edges are smoothed with a file or the like.

[0064] The mouthpiece of the first embodiment is shaped to cover part of the gums on the vestibular side of the oral cavity, and is the same as the conventional manufacturing method except that in the finishing stage of the manufacturing method of the above-mentioned mouthpiece, more of the outer periphery (base edge) of the mouthpiece is left than in the conventional method.

[0065] In recent years, 3D printing technology, in which teeth alignment data (STL data) taken with an intraoral scanner is printed to produce a mouthpiece, has become popular, and mouthpieces made using 3D printing technology are used for orthodontic treatment.

[0066] When the mouthpiece of the first embodiment is manufactured using a 3D printer, a powder raw material or liquid raw material in which the surface-modified zinc oxide powder is uniformly mixed with a resin base material is used. When using 3D printing technology, the process is the same as creating a mouthpiece using a conventional 3D printer, except that the length of the base edge is designed to be long enough to cover part of the gums.

[0067] There is no particular limitation on the resin for 3D printing that can contain surface-modified zinc oxide, but examples include filaments for fused deposition modeling, resins for stereolithography, and the like. Commercially available fused deposition model filaments or stereolithography resins (resin materials) include, for example, those manufactured by FLASHFORGE that can be used as dental materials, iMAS SG & Trays (manufactured by YAMAKIN Corporation), NextDent Orthorigid (manufactured by Denken-Hi Dental), Deema Print Splints (manufactured by Kulzer GmbH), and resins for 3D print splints (manufactured by Machine Tool Chuo Corporation). The above commercially available filaments or resins capable of being formed into filaments can be melted, and a masterbatch containing a high concentration of surface-modified zinc oxide is added to produce a uniformly mixed pellet. This can then be reshaped into a filament, allowing it to be used for 3D printing using the fused deposition modeling method.

[0068] 5. Method for manufacturing the mouthpiece according to the second embodiment The mouthpiece of the second embodiment differs from conventional mouthpiece manufacturing methods and the mouthpiece manufacturing method of the first embodiment in that the mouthpiece of the second embodiment is composed of a first layer which is an inner layer and a second layer which is an outer layer.

[0069] In the method of pressure molding (pressing) a resin plate (resin sheet) made of a resin material for a mouthpiece, a resin plate that will become the first layer and a resin plate that will become the second layer are stacked and pressure molded, or each layer can be pressure molded in turn. If necessary, a third layer having the function of adhering the first and second layers is sandwiched between the resin plates that will become the first layer and the second layer and then pressure molded, or the first layer and the second layer are each pressure molded, and then the material for the third layer, such as an adhesive, is sandwiched between them and then pressure is applied.

[0070] The adhesive is not particularly limited, and any adhesive that can bond the first layer and the second layer, does not lose its adhesive strength due to moisture such as saliva, and does not have any adverse effects on the human body may be used. Commercially available adhesives that can be used include Entofitter (manufactured by Elcodent Co., Ltd.).

[0071] Here, one or both of the resin plates constituting the first layer and the second layer is a resin plate containing surface-modified zinc oxide. The resin plates constituting the first layer and the second layer may be formed from different resins. Furthermore, when either or both of the first layer and the second layer have a shape that covers up to a part of the gums, they may be manufactured in accordance with the manufacturing method of the mouthpiece of the first embodiment described above.

[0072] When manufacturing the mouthpiece of the second embodiment using 3D printing technology, it is possible to print the first layer (inner layer) using the powder or liquid raw material for forming the first layer, then exchange it for the powder or liquid raw material for forming the second layer, and print the second layer (outer layer). When forming the third layer (middle layer), it is possible to form the third layer by exchanging the powder or liquid raw material for forming the third layer for bonding the first layer and the second layer after forming the first layer, and then form the second layer.

[0073] 6. Mouthpiece making kit for treating periodontal disease and peri-implantitis The kit for treating periodontal disease or peri-implantitis of the present invention comprises: The mouthpiece according to the first or second aspect, and A topical agent containing an antibacterial agent against periodontal disease-causing bacteria The present invention is characterized by comprising:

[0074] The "mouthpiece of the first or second embodiment" in the above kit may be formed from a resin plate for pressure molding containing surface-modified zinc oxide, or may be formed by 3D printing.

[0075] The agent is not particularly limited as long as it has antibacterial properties against periodontal disease-causing bacteria, but is preferably chicken blood wilt or an extract thereof. Chicken-eye grape has a strong inhibitory effect on osteoclast differentiation and survival. Furthermore, Chicken-eye grape has preventive and therapeutic effects on periodontal disease, especially peri-implantitis.

[0076] "Chicken Blood Wisteria" is a well-known herbal medicine, such as Spatholobus suberectus Dunn, S.harmandii Gagnep, S.sinensis Chun et T,Chen, Millettia dielsiana Harms, M. nitida Benth. var. hirsutissima Z., which belong to the Fabaceae family. Wei), M. gentiliana Level, M. speciosa Champ., M. reticulata benth, Mucuna sempervirens Hemsl., M. birdwoodiana Tutcher, M. castanea Merr, Craspedolobium schochii Harms), Kadsura interior AC Smith, K. heteroclita (Roxb.) Craib, and Schisandra propinqua (Wall.) Baill. var. sinensis Oliv., all of which belong to the family Schisandraceae.

[0077] In the present invention, the dried stems, vines, and roots of the above-mentioned various plants may be used as they are, or may be cut or crushed, or an extract obtained by contacting the dried stems, vines, and roots of the above-mentioned plants with an appropriate solvent (e.g., water or hot water) may be used. The form of the extract is not particularly limited, and liquid, soft extract, powder, granules, etc. may be used.

[0078] The "extract of henbits" can be produced, for example, as follows. The dried stems, vines, and roots of the Japanese laurel wort are brought into contact with water, hot water, or an organic solvent such as alcohol, and heated as necessary to extract the extract. Alternatively, the extract may be extracted by a supercritical extraction method. The concentration of the sclerotinia component in the extract of sclerotinia may be adjusted as necessary, but for example, it can be adjusted to 20% by adding 200 g of dried sclerotinia to 1 L of water and heating. The resulting 20% ​​extract can be further diluted as necessary for use. The extract of Oriental ginseng may be further concentrated to give an extract, or may be freeze-dried to give a powder or granules.

[0079] According to the present invention, by using a combination of an application agent containing Phyllanthus or an extract thereof and a mouthpiece that covers part of the gums, the active ingredients of Phyllanthus can be retained at the base of the teeth for a long period of time, and the effects can be sustained.

[0080] Using the kit of the present invention, an application agent containing sclerotinia gracilis or an extract thereof is applied to the inside of the mouthpiece that comes into contact with the dentition, and the mouthpiece is then attached to the dentition. Since henbituari does not irritate or irritate the gingival mucosa, it can remain in contact with the teeth and gums for a long time. There is no need for special processing such as creating a reservoir inside the mouthpiece to hold the medicine. According to the mouthpiece of the present invention, which covers part of the gums, the medicine can reach the periodontal pocket sufficiently, and a higher preventive and therapeutic effect against periodontal disease and peri-implant inflammation can be expected. EXAMPLES

[0081] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0082] <Production of resin plate containing surface-modified zinc oxide> Manufacturing Example 1-1 The resin material used in the mouthpiece, ethylene-vinyl acetate copolymer (EVA), was heated to soften it, and then surface-modified zinc oxide powder (AD-PSJ; manufactured by ADX Co., Ltd.) was added to a final concentration of 1% by mass and mixed uniformly. The obtained resin material containing the surface-modified zinc oxide was formed into a sheet having a thickness of 1 mm to obtain a resin plate containing the surface-modified zinc oxide.

[0083] Manufacturing Example 1-2 Polyethylene terephthalate (PET), the resin material used in the mouthpiece, was heated to soften it, and then surface-modified zinc oxide powder (AD-PSJ; manufactured by ADX Co., Ltd.) was added to a final concentration of 1% by mass and mixed uniformly. The obtained resin material containing the surface-modified zinc oxide was formed into a sheet having a thickness of 1 mm to obtain a resin plate containing the surface-modified zinc oxide.

[0084] <Production of resin liquid for 3D printing containing surface-modified zinc oxide> Manufacturing Example 2 To manufacture 3D printing resin containing surface-modified zinc oxide, surface-modified zinc oxide powder was added to a liquid resin material (EVA) used as a resin material for dental occlusal splints to a final concentration of 1% by mass, and mixed uniformly.

[0085] <Production of the mouthpiece according to the first embodiment> Example 1-1: Pressure welding A working plaster model was made by pouring plaster into the impression material of the properly taken dentition. The base surface of the plaster model was horizontal, and sharp parts were ground down in advance. The surface-modified zinc oxide-containing EVA resin plate (resin sheet) manufactured in Manufacturing Example 1-1 was heated and softened, then placed on the plaster model and pressed against it under suction. At this time, the base surface was set perpendicular to the tooth axis of the anterior teeth so that the thickness of the pressed sheet (mouthpiece) would be constant. After cooling, the mouthpiece was removed from the model and the length of the base edge was trimmed to a height that covered the periodontal pocket, after which adjustment and polishing were carried out to complete the mouthpiece. Photographs of the obtained mouthpiece are shown in Figures 1A and 1B.

[0086] Example 1-2: Pressure welding A working plaster model was prepared in the same manner as in Example 1-1. Undercuts were blocked out of this plaster model with plaster, room temperature polymerizing resin, or wax, and an impression was taken with a silicone impression material. Plaster was poured into the model to produce a duplicate. The surface-modified zinc oxide-containing PET resin plate (resin sheet) manufactured in Manufacturing Example 1-2 was heated and softened, then placed on the replica model and pressed against it while being sucked. In this case, the base surface was set to be perpendicular to the tooth axis of the anterior teeth in the same manner as in Example 1-1, so that the thickness of the pressed sheet (mouthpiece) was constant. After cooling, the mouthpiece was removed from the model and the length of the base edge was trimmed to a height that covered the periodontal pocket, after which adjustment and polishing were carried out to complete the mouthpiece.

[0087] Example 1-3: 3D printing Using dentition data (STL data) scanned with an intraoral scanner or dentition data (STL data) obtained by scanning a dentition model, a mouthpiece was manufactured with a 3D printer. The 3D printing resin manufactured in Manufacturing Example 2 was placed in a liquid tank, and a UV laser was irradiated from the top or bottom toward the liquid surface to harden and harden each layer, forming a layered mouthpiece. The process was the same as manufacturing a mouthpiece using a normal 3D printer, except that the 3D printing data was set so that the length of the base edge was high enough to cover the periodontal pocket.

[0088] <Production of the mouthpiece according to the second embodiment> Example 2-1: Pressure welding A working plaster model was made by pouring plaster into the impression material of the properly taken dentition. The base surface of the plaster model was horizontal, and sharp parts were ground down in advance. In addition, the base surface was set perpendicular to the tooth axis of the anterior teeth so that the thickness of the pressed sheet (mouthpiece) would be uniform. The surface-modified zinc oxide-containing EVA resin plate (resin sheet) produced in Production Example 1-1 was heated and softened, and then placed on the plaster model and pressed against it under suction to form a first layer. Next, an adhesive was applied to the surface of the formed first layer that was not in contact with the teeth row, and the surface-modified zinc oxide-containing PET resin plate (resin sheet) produced in Production Example 1-2 was pressed onto the first layer in the same manner as the first layer, and pressure-molded to form the second layer. After cooling, the sheet was removed from the stone model, trimmed, and polished to produce a mouthpiece having a first layer (EVA) and a second layer (PET) containing surface-modified zinc oxide. A photograph of the obtained mouthpiece is shown in Figure 3.

[0089] Test example: Observation of changes in cervical bacterial counts after wearing a night guard (material) The following tests were conducted using a night guard (mouthpiece of the first embodiment) shown in Figure 4A, which was prepared in the same manner as in Example 1-1 and contains 1% by mass of surface-modified zinc oxide and has a shape that covers up to a portion of the gums, and a night guard (comparative example) shown in Figure 4B, which does not contain surface-modified zinc oxide and has a shape that covers up to a portion of the gums.

[0090] (method) The night before going to bed, the subjects brushed their teeth, wore the night guard, went to bed, and measured the number of bacteria when they woke up. Since the test was conducted on a single subject, the subject wore a night guard (comparative example) that did not contain surface-modified zinc oxide on the first day, and a night guard (mouthpiece of the first embodiment) that contained 1% by mass of surface-modified zinc oxide on the second day.

[0091] Immediately after waking up, the night guard was removed and cervical plaque was collected with a sterile cotton swab. The collected plaque was suspended in phosphate buffered saline and serially diluted 10-fold. The obtained diluted solution was smeared onto BHI-YHK blood agar medium (BHI; Becton Dickinson and Company) supplemented with yeast extract (5 mg / mL), hemin (5 μg / mL), vitamin K1 (1 μg / mL) and 5% defibrinated sheep blood, Mitis-Salivarius agar (MS medium; Becton Dickinson and Company), and Sabouraud agar medium (Nissui Pharmaceutical Co., Ltd.).

[0092] The BHI-YHK blood agar medium and Mitis-MS medium were cultured for 7 days at 37°C in an anaerobic box filled with anaerobic gas (70% N2, 15% H2, 15% CO2), and the Sabouraud agar medium was cultured for 7 days at 37°C under aerobic conditions, after which the viable bacterial count (cfu / mL) was calculated. The results are shown in Table 1.

[0093] [Table 1]

[0094] As shown in Table 1, the total number of bacteria in the cervical plaque on the morning after wearing a night guard containing 1% by mass of surface-modified zinc oxide (mouthpiece of the first embodiment) was reduced by about 60% compared to wearing a night guard not containing surface-modified zinc oxide (comparative example). There was no significant change in the number of oral streptococci. The number of fungi was reduced by about 40%.

[0095] In addition, the collected dental plaque was suspended in phosphate buffered saline for 10 min. -6 Gram staining was performed on a plate medium smeared with the 2x diluted solution, and it was confirmed that all bacteria were gram positive when the mouthpiece containing surface-modified zinc oxide was used. In the same manner, Gram staining was performed on a mouthpiece not containing surface-modified zinc oxide (comparative example), both gram positive and gram negative bacteria were confirmed, whereas gram negative bacteria were significantly reduced. The total number of bacteria was reduced by about half, which is thought to be due to the suppression of gram negative bacteria with thin cell walls.

[0096] The oral cavity is a complex environment in which many types of bacteria coexist, and the types and proportions of these bacteria, especially the balance between gram-negative and gram-positive bacteria, are important factors for maintaining the oral cavity's immune system, i.e., the bacteriostatic environment.

[0097] When gram-negative bacteria become predominant, periodontal disease, dental caries, bad breath, etc., occur or become more likely to worsen. In particular, almost all periodontal disease bacteria are gram-negative bacteria, and when the balance of oral bacteria is disrupted and gram-negative bacteria become predominant, it creates an environment in which periodontal disease is more likely to worsen. Inhibiting the proliferation of gram-negative bacteria means that the proliferation of bacteria involved in periodontal disease is also inhibited, and the worsening of periodontal disease can be inhibited.

[0098] It was found that a night guard that did not contain surface-modified zinc oxide (comparative example) was unable to suppress the growth of gram-negative bacteria and may have the potential to worsen the oral environment, whereas a night guard that contained surface-modified zinc oxide suppressed the growth of gram-negative bacteria and created a bacteriostatic environment in the mouth.

[0099] In the case of elderly people and diabetics with a background of systemic immunosuppression, the total number and balance of bacteria in the oral cavity have a particularly large impact on health. By using a night guard containing surface-modified zinc oxide, it is expected that the total number of bacteria can be reduced and the balance of bacteria in the oral cavity can be kept healthy, that is, a bacteriostatic environment can be maintained. This can prevent not only oral frailty but also systemic frailty.

[0100] Furthermore, from the above test results, it was confirmed that the night guard containing surface-modified zinc oxide (mouthpiece of the first embodiment) has a shape that covers part of the gums, but even under conditions in which the dentition and gums are likely to be in an anaerobic environment, such as during sleep, the inclusion of surface-modified zinc oxide makes it possible to inhibit or bacteriostatically inhibit the growth of bacteria, including mutans streptococci and Candida fungi, which are the main constituents of plaque and denture plaque. This shows that the mouthpiece of the first embodiment can inhibit the formation of plaque and denture plaque.

[0101] Furthermore, by preventing an increase in plaque-forming bacteria, an anaerobic environment caused by plaque is less likely to be formed, and the proliferation of periodontal disease bacteria, such as Prophyromonas gingivalis, which are obligate anaerobes, is suppressed, which is thought to prevent the onset of periodontal disease and slow its progression. It is also possible to prevent, inhibit the progression of, and improve denture stomatitis, which is known to be caused by Candida fungi, including Candida albicans, the main component of denture plaque. [Industrial Applicability]

[0102] The mouthpiece of the present invention is particularly useful in the field of dental treatment, for treating caries, periodontal disease, malocclusion, etc., in the field of cosmetic dentistry, such as orthodontics and tooth bleaching, and in the field of treatment of stomatitis, temporomandibular joint disorders, etc. Furthermore, it is useful for dental treatment using a mouthpiece, for example, treatment of periodontal disease, treatment of peri-implantitis, and preparation of an immune, i.e., bacteriostatic environment, in the oral cavity before implant placement. Furthermore, the mouthpiece of the present invention is useful not only in the medical field, but also in the field of sports.

Claims

1. A mouthpiece for use by being attached to the dentition of a human or mammal, It can cover a part or all of the dentition and a part of the gingiva on the oral vestibule side continuing from the part or all of the dentition, A mouthpiece containing surface-modified zinc oxide.

2. A mouthpiece for use by being attached to the dentition of a human or mammal, a first layer in contact with the dentition; and a second layer on a surface opposite to a surface of the first layer that contacts the tooth row; A mouthpiece, wherein one or both of the first and second layers contain surface-modified zinc oxide.

3. The mouthpiece according to claim 1 or 2, wherein the zinc oxide powder has an average particle size in the range of 1 to 500 nm.

4. The mouthpiece according to claim 1 or 2, wherein the surface modification is coating with a zinc sulfide film.

5. The mouthpiece according to claim 1 or 2, wherein the surface modification is a coating with a coupling agent.

6. The mouthpiece according to claim 1 or 2, wherein the surface modification is a partial coating of the zinc oxide powder surface.

7. The mouthpiece according to claim 1 or 2, wherein the coating amount of the zinc sulfide or the coupling agent is 0.1 to 30% by mass.

8. The mouthpiece according to claim 1 or 2, wherein the amount of the surface-modified zinc oxide powder is 0.1 to 10% by mass.

9. The mouthpiece according to claim 1 or 2, which inhibits the proliferation of bacteria causing periodontal disease, bacteria causing dental caries, and / or fungi.

10. The mouthpiece according to claim 1 or 2, which inhibits the adhesion of denture plaque.

11. The mouthpiece according to claim 1 or 2, which reduces substances that cause bad breath.

12. 3. The mouthpiece according to claim 1 or 2, which is for treating or preventing peri-implantitis.

13. 3. The mouthpiece according to claim 1 or 2, which is used either before or after implant installation, or both.

14. 2. The mouthpiece according to claim 1, which is made of a material having rubber elasticity.

15. The mouthpiece according to claim 1, wherein the material having rubber elasticity comprises one or more selected from the group consisting of ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU).

16. The mouthpiece according to claim 2 , wherein the first layer is made of a material different from the second layer.

17. The mouthpiece according to claim 2 , wherein the first layer is made of a material having rubber elasticity.

18. The mouthpiece according to claim 2, wherein the first layer is made of a material including one or more selected from the group consisting of ethylene-vinyl acetate copolymer (EVA) and thermoplastic polyurethane (TPU).

19. The mouthpiece of claim 2 , wherein the second layer is made of a material having a higher rigidity than the material constituting the first layer.

20. The mouthpiece of claim 2, wherein the second layer is made of a material including one or more selected from the group consisting of polyethylene terephthalate (PET) and polyethylene terephthalate glycol (PETG).

21. The mouthpiece of claim 2, wherein the first layer, or the first layer and the second layer, cover a portion or all of the dentition and a portion of the gingiva on the vestibular side of the oral cavity continuing from the portion or all of the dentition.

22. The mouthpiece according to claim 1 or 2, and A topical agent containing an antibacterial agent against periodontal disease-causing bacteria A kit for treating periodontal disease or peri-implantitis comprising:

23. The kit for treating periodontal disease or peri-implantitis according to claim 22, wherein the drug is henbit or an extract thereof.

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