Invisible appliance for treating periodontal disease and preventing enamel demineralization and preparation method thereof

Abstract

The embodiment of the invention provides an invisible appliance for treating periodontal disease and preventing enamel demineralization and a preparation method of the invisible appliance. The invisible appliance comprises a tooth socket, a quaternary ammonium salt antibacterial agent, a remineralizing agent coating and a waterborne polyurethane protruding point-shaped coating capable of releasing periodontal drugs, wherein the periodontal drug is a PDE4 receptor inhibitor.

Description

Technical Field

[0001] The present specification relates to the fields of oral orthodontics and periodontology, and in particular to an invisible orthodontic appliance for treating periodontal disease and preventing enamel demineralization and a preparation method thereof. Background Art

[0002] The main symptoms of periodontal disease patients include bleeding gums, loose teeth, reduced alveolar bone height, gingival recession, the appearance of "black triangles", etc. In severe cases, the teeth are fan-shaped, causing tooth protrusion and occlusal trauma, which further leads to alveolar bone absorption. Orthodontic treatment can alleviate a series of problems caused by periodontal disease.

[0003] During orthodontic treatment, orthodontic appliances need to be worn in the mouth, which can make teeth difficult to clean and cause plaque accumulation, and further cause complications such as enamel demineralization, caries, and periodontal disease. Compared with traditional braces, bracketless invisible braces are comfortable, beautiful, and easy to wear and take off. However, invisible braces completely wrap the teeth when worn, and the polymer material surface of invisible braces is prone to plaque adhesion, which also increases the risk of complications such as enamel demineralization, caries, and periodontal disease.

[0004] Commonly used antimicrobial agents include inorganic antimicrobial agents (such as metal ions and their oxides), organic antimicrobial agents (such as quaternary ammonium salts), natural antimicrobial agents (such as chitin), etc. However, adding antimicrobial agents to the membrane surface of braces or braces still has problems such as short antimicrobial release time, easy aging of braces, and poor stability. Drug treatments for periodontal disease include systemic and local medications. Systemic medications have greater toxic side effects on the whole body, and the drug concentration acting on the local gums is low. Local medications are applied intraorally, and the local drug concentration is higher, but the doctor needs to perform multiple intraoral medication operations, which takes longer and brings inconvenience to the patient.

[0005] Therefore, it is desirable to provide an invisible orthodontic appliance that can treat periodontal disease and has antibacterial and remineralization functions. Summary of the invention

[0006] One or more embodiments of the present specification provide an invisible braces for treating periodontal disease and preventing enamel demineralization, the invisible braces comprising: braces, a quaternary ammonium salt antibacterial agent, a remineralizer coating, and an aqueous polyurethane protrusion dot coating capable of releasing periodontal drugs; the periodontal drug is a PDE4 receptor inhibitor.

[0007] In some embodiments, the PDE4 receptor inhibitor is roflumilast, celecoxib, or apremilast.

[0008] In some embodiments, the quaternary ammonium salt antibacterial agent is grafted onto the surface of the brace in contact with the tooth surface; the aqueous polyurethane protrusion dot-shaped coating capable of releasing periodontal drugs is on the inner side of the brace in contact with the tooth.

[0009] One or more embodiments of the present specification provide a method for preparing an invisible brace for treating periodontal disease and preventing enamel demineralization, the method comprising: S1, using a film to make a dental brace; S2, photopolymerizing and grafting a quaternary ammonium salt antibacterial agent on the inner surface of the dental brace at room temperature to obtain a dental brace containing the quaternary ammonium salt antibacterial agent; S3, adding a water-based polyurethane protrusion dot coating capable of releasing a PDE4 receptor inhibitor to the inner side of the dental brace containing the quaternary ammonium salt antibacterial agent obtained in step S2, which is in contact with the teeth, to obtain the invisible brace for treating periodontal disease and preventing enamel demineralization.

[0010] In some embodiments, the membrane used to make the braces is a multilayer structure of at least two layers, wherein the layer closest to the tooth surface is made of thermoplastic polyurethane (TPU), and the remaining layers can be any material selected from polyethylene terephthalate-1,4-cyclohexanedimethanol (PETG), thermoplastic polyurethane (TPU), polycarbonate (PC), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (EVA), and polyamide (PA).

[0011] In some embodiments, a remineralizing agent is blended with the TPU material to make the membrane.

[0012] In some embodiments, the multilayer film of the braces is produced by a co-extrusion method, including: collecting a scan model of the subject's oral cavity, 3D printing a tooth model after computer design, using a vacuum laminator to heat the film until it softens, and then vacuum adsorbing it onto the tooth model, and then using laser cutting or manual trimming to cut the shape of the gum edge to produce the braces.

[0013] In some embodiments, the photopolymerization grafting of the quaternary ammonium salt antibacterial agent comprises: immersing the dental cap in a quaternary ammonium salt antibacterial agent grafting solution for 30 minutes, and irradiating the dental cap contacting the tooth side with ultraviolet light for 30 minutes.

[0014] In some embodiments, the method for preparing the quaternary ammonium salt antibacterial agent grafting liquid includes: weighing 2-5% of the weight of the braces of anthraquinone and 2% of the weight of the braces of a quaternary ammonium salt antibacterial agent in anhydrous ethanol, stirring for 30 minutes using a magnetic stirring device to obtain the quaternary ammonium salt antibacterial agent grafting liquid.

[0015] In some embodiments, the protruding dot-shaped coating includes: a photocurable water-based polyurethane containing a PDE4 receptor inhibitor; the preparation method of the photocurable water-based polyurethane containing a PDE4 receptor inhibitor includes: diluting the water-based polyurethane coating liquid with anhydrous ethanol to a polyurethane coating liquid with a content of 10%, adding 5% of the total mass of the water-based polyurethane coating liquid as a photoinitiator LAP and 20 μmol / ml of a PDE4 receptor inhibitor to obtain the photocurable water-based polyurethane containing a PDE4 receptor inhibitor.

[0016] In some embodiments, the method for preparing the aqueous polyurethane coating solution comprises:

[0017] (a) Acetone, isophorone diisocyanate (IPDI), polylactic acid polyol (PLA-OH Ma=2000), polycarbonate diol (PCDL Mn=1000), and 5% dibutyltin dilaurate (DBTDL) were added to a three-necked round-bottom flask equipped with a mechanical stirrer and a condenser and reacted at 80°C for 2 h;

[0018] (b) adding the chain extender dimethylaminopropylamine diisopropyl alcohol (DPA) and continuing the reaction for 3 h;

[0019] (c) then cooling to 65° C., adding hydroxyethyl acrylate (HEA) and a small amount of DBTDL, and reacting for 4 hours;

[0020] (d) cooling the reaction system to 60° C. and adding methanol until the -NCO in the system is completely reacted;

[0021] (e) Deionized water was added to the flask, CO2 gas was introduced at 1000 rpm for 1 hour under high-speed stirring, and acetone was removed under vacuum for 1 hour to obtain the waterborne polyurethane coating solution.

[0022] In some embodiments, the preparation reaction of the aqueous polyurethane coating solution is carried out in N2. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] This specification will be further described in the form of exemplary embodiments, which will be described in detail by the accompanying drawings. These embodiments are not restrictive, and in these embodiments, the same number represents the same structure, wherein:

[0024] Figure 1 is a schematic diagram of an invisible brace for treating periodontal disease and preventing enamel demineralization according to some embodiments of the present specification;

[0025] Figure 2 is a schematic diagram of a water-based polyurethane protrusion dot coating capable of releasing periodontal drugs according to some embodiments of the present specification;

[0026] Figure 3It is a schematic diagram of a mold for adding a periodontal drug protrusion dot coating according to some embodiments of this specification;

[0027] Figure 4 It is a flow chart of a method for preparing an invisible brace for treating periodontal disease and preventing enamel demineralization according to some embodiments of this specification;

[0028] Figure 5 It is an infrared spectrum of a dental cap containing a DMADDM quaternary ammonium salt antibacterial agent according to some embodiments of this specification;

[0029] Figure 6 It is a bar chart showing the expression of Tnf-α after mouse macrophages were cultured with Roflumilast culture medium of different concentrations as shown in some examples of this specification. DETAILED DESCRIPTION

[0030] In order to more clearly illustrate the technical solutions of the embodiments of this specification, the following is a brief introduction to the drawings required for the description of the embodiments. Obviously, the drawings described below are only some examples or embodiments of this specification. For ordinary technicians in this field, this specification can also be applied to other similar scenarios based on these drawings without creative work. Unless it is obvious from the language environment or otherwise explained, the same reference numerals in the figures represent the same structure or operation.

[0031] It should be understood that the "system", "device", "unit" and / or "module" used herein are a method for distinguishing different components, elements, parts, portions or assemblies at different levels. However, if other words can achieve the same purpose, the words can be replaced by other expressions.

[0032] As shown in this specification and claims, unless the context clearly indicates an exception, the words "a", "an", "an" and / or "the" do not refer to the singular and may also include the plural. Generally speaking, the terms "comprise" and "include" only indicate the inclusion of the steps and elements that have been clearly identified, and these steps and elements do not constitute an exclusive list. The method or device may also include other steps or elements.

[0033] Flowcharts are used in this specification to illustrate the operations performed by the system according to the embodiments of this specification. It should be understood that the preceding or following operations are not necessarily performed precisely in order. Instead, the steps may be processed in reverse order or simultaneously. At the same time, other operations may also be added to these processes, or one or more operations may be removed from these processes.

[0034] One embodiment of the present specification provides an invisible brace for treating periodontal disease and preventing tooth enamel demineralization. The invisible brace comprises a dental brace, a quaternary ammonium salt antibacterial agent, a remineralizing agent coating, and a high elastic modulus waterborne polyurethane protrusion dot coating capable of releasing periodontal drugs.

[0035] Periodontal disease refers to a disease that occurs in the periodontal tissue. The periodontal tissue is also called the supporting tissue of the teeth. The periodontal tissue includes three parts: alveolar bone, gums, and periodontal membrane. In some embodiments, periodontal disease may include gum disease and periodontitis. The main manifestations of periodontal disease include gingival inflammation, bleeding gums, loose teeth, and chewing weakness. The worsening of periodontal disease will impair the oral chewing function and even endanger physical health.

[0036] Tooth enamel refers to the white, translucent tissue on the outermost layer of teeth. Tooth enamel is the hardest part of the tooth and is composed of inorganic substances such as calcium and phosphorus. It is wear-resistant and corrosion-resistant, and can protect teeth from damage. Tooth enamel demineralization refers to the loss of calcium and phosphorus on the surface of tooth enamel. Tooth enamel demineralization can cause damage to the health of teeth. For example, white patches may appear on the teeth, and in severe cases, depressions may appear on the tooth surface, leading to tooth decay.

[0037] The braces are the main structural part of the invisible braces, which are used to fix the patient's teeth. In some embodiments, the braces can be prepared in a variety of ways. In some embodiments, the braces can be prepared by 3D printing technology. For example, a technician can generate a 3D tooth model of the patient by digital scanning, print out the tooth model using 3D printing technology, and use a hot pressing film material to perform vacuum hot pressing molding on the tooth model to obtain the braces.

[0038] Quaternary ammonium antimicrobial agents rely on the positively charged quaternary ammonium group to rupture the negatively charged bacterial cell membrane, thereby achieving a bactericidal effect.

[0039] Remineralizing agents refer to agents that promote the remineralization of tooth enamel. In some embodiments, remineralizing agents may include calcium compounds, phosphorus compounds, and fluorine compounds, etc. In some embodiments, calcium compounds may include calcium chloride, calcium citrate, calcium hydroxyapatite, calcium carbonate, calcium oxalate, etc., or mixtures thereof. In some embodiments, phosphorus compounds may include calcium hydrogen phosphate, calcium phosphate, potassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, magnesium phosphate, etc., or mixtures thereof. In some embodiments, fluorine compounds may include fluoroapatite, calcium fluoride, potassium hydrogen fluoride, etc., or mixtures thereof.

[0040] Waterborne polyurethane is a type of polyurethane system that uses water instead of organic solvents as solvent.

[0041] As used herein, periodontal drugs refer to drugs used to treat periodontal disease, such as Xipayi Gum Solution, tetracycline drugs, minocycline hydrochloride, metronidazole sustained-release agent, povidone-iodine, Kangfuxin solution, PDE4 receptor inhibitors, and the like.

[0042] In some embodiments, the periodontal drug is a PDE4 receptor inhibitor.

[0043] PDE4 receptor inhibitors refer to agents that inhibit the activity of phosphodiesterase 4 (PDE4). PDE4 can degrade intracellular cyclic adenosine monophosphate (cAMP). In some embodiments, the level of intracellular cAMP can affect inflammatory cell pathways. In some embodiments, the increase in intracellular cAMP can inhibit the release of inflammatory cytokines. PDE4 receptor inhibitors play an anti-inflammatory role by inhibiting the activity of PDE4, resulting in an increase in intracellular cAMP.

[0044] In some embodiments, the PDE4 receptor inhibitor may be Roflumilast.

[0045] In some embodiments, the PDE4 receptor inhibitor may also be celecoxib or apremilast.

[0046] In some embodiments, the quaternary ammonium antibacterial agent is grafted onto the surface of the entire inner side of the braces that is in contact with the tooth surface, so that the entire dentition can be exposed to the quaternary ammonium antibacterial agent on the surface of the braces to reduce bacteria attached to the braces and tooth surfaces and avoid the formation of white spots and caries on the tooth surface.

[0047] Invisible braces for treating periodontal disease and preventing enamel demineralization Figure 1 In some embodiments, a water-based polyurethane protrusion dot coating capable of releasing periodontal drugs is added to the inner side of the braces that is in contact with the teeth within 5 mm from the bottom edge of the braces. The water-based polyurethane protrusion dot coating capable of releasing periodontal drugs on the invisible braces is as shown in FIG. Figure 2 As shown, Figure 3 A mold for adding periodontal drugs with protruding dot-shaped coatings. The thickened coating can thicken the bottom edge of the braces, increase the pressure on the neck of the tooth, and help control the movement of the tooth root. At the same time, adding periodontal drugs at the neck of the tooth close to the gingival edge can help control periodontal inflammation. The coating containing periodontal drugs can still expose the lower antibacterial and remineralizing agent coatings, which does not affect the contact between the antibacterial and remineralizing agents and the teeth, and effectively prevents white spots and caries at the neck of the tooth.

[0048] The invisible braces provided in the embodiments of this specification contain quaternary ammonium salt antibacterial agents and remineralizing agents, which can effectively reduce bacteria attached to the surface of braces and teeth, and can prevent enamel demineralization, a major complication of orthodontics; quaternary ammonium salts are grafted on the surface of braces that are in contact with the tooth surface, solving the problems of easy shedding of surface coatings and short maintenance time of unstable antibacterial agent blends. The invisible braces provided in the embodiments of this specification also have a high elastic modulus aqueous polyurethane protrusion dot-shaped coating that can release periodontal drugs at the position where the edge of the braces contacts the edge of the gums. The coating can release drugs at the inflamed site and effectively fight inflammation; the coating is made of aqueous polyurethane material, which is skin-friendly and soft, making the braces more comfortable to wear.

[0049] Figure 4 This is a flow chart of a method for preparing an invisible brace for treating periodontal disease and preventing tooth enamel demineralization according to some embodiments of the present specification, comprising: S1, using a membrane to make a brace; S2, photopolymerizing and grafting a quaternary ammonium antibacterial agent on the inner surface of the brace at room temperature to obtain a brace containing a quaternary ammonium antibacterial agent; S3, adding a protruding dot-shaped coating containing a PDE4 receptor inhibitor to the inner side of the brace containing the quaternary ammonium antibacterial agent obtained in step S2, which is in contact with the tooth, to obtain an invisible brace for treating periodontal disease and preventing tooth enamel demineralization.

[0050] In some embodiments, the membrane of the mouthpiece can be a multi-layer structure of at least two layers. In some embodiments, the membrane of the mouthpiece can be a double-layer structure. In some embodiments, the membrane of the mouthpiece can be a three-layer structure.

[0051] In some embodiments, the membrane material of the mouthpiece may include a thermoplastic polymer material.

[0052] In some embodiments, the material of the layer of the dental brace film closest to the tooth surface can be thermoplastic polyurethane (TPU). In some embodiments, the other layers of the dental brace film can be any material selected from polyethylene terephthalate-1,4-cyclohexanedimethanol (PETG), thermoplastic polyurethane (TPU), polycarbonate (PC), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (EVA), and polyamide (PA).

[0053] In some embodiments, the remineralizing agent is blended with the TPU material to make the membrane.

[0054] In some embodiments, the multi-layer membrane of the mouthpiece can be made by a variety of methods.

[0055] In some embodiments, the multilayer film of the braces can be made by a co-extrusion method. The method may include the following steps: collecting a scanned model of the subject's oral cavity, 3D printing a tooth model after computer design, using a vacuum laminator to heat the film until it softens, and then vacuum adsorbing it onto the tooth model, and then cutting the shape of the gum edge by laser cutting or manual trimming to make the braces.

[0056] In some embodiments, the intraoral scan model can be acquired by a scanner equipped with a probe, such as a dental 3D scanner.

[0057] In some embodiments, photopolymerizing and grafting a quaternary ammonium antibacterial agent on the inner surface of a brace at room temperature includes: immersing the brace in a quaternary ammonium antibacterial agent grafting solution for 30 minutes, irradiating the side of the brace contacting the tooth with ultraviolet light for 30 minutes, then removing the brace from the grafting solution, ultrasonically cleaning it with anhydrous ethanol and deionized water alternately for 5 minutes for a total of 3 times, and drying it to constant weight at room temperature.

[0058] Photopolymerization grafting refers to a grafting reaction in which a photoinitiator initiates polymerization of monomers under illumination conditions. In some embodiments, the illumination conditions may include visible light and invisible light. In some embodiments, the illumination conditions may be ultraviolet light. A photoinitiator, also known as a photosensitizer, refers to a substance that can initiate polymerization upon illumination. In some embodiments, the photoinitiator may include a free radical photoinitiator and a cationic photoinitiator, etc. In some embodiments, the monomer may be a small molecule substance that can undergo polymerization. In some embodiments, the monomer may be DMADDM.

[0059] As used herein, the quaternary ammonium salt antibacterial agent grafting liquid is used to graft the quaternary ammonium salt antibacterial agent onto the inner surface of the brace.

[0060] In some embodiments, the preparation method of the quaternary ammonium salt antibacterial agent grafting liquid may include the following steps: weighing 2-5% of the weight of anthraquinone and 2% of the weight of the braces into anhydrous ethanol, stirring for 30 minutes using a magnetic stirring device to obtain the quaternary ammonium salt antibacterial agent grafting liquid.

[0061] In some embodiments, the waterborne polyurethane protrusion dot coating containing a PDE4 receptor inhibitor comprises: a photocurable waterborne polyurethane containing a PDE4 receptor inhibitor.

[0062] In some embodiments, the preparation method of a photocurable waterborne polyurethane containing a PDE4 receptor inhibitor includes: diluting an aqueous polyurethane coating liquid with anhydrous ethanol to a polyurethane coating liquid with a content of 10%, adding a photoinitiator LAP with a total mass of 5% of the aqueous polyurethane coating liquid and 20 μmol / ml of a PDE4 receptor inhibitor to obtain a photocurable waterborne polyurethane containing a PDE4 receptor inhibitor.

[0063] As mentioned above, waterborne polyurethane is a type of polyurethane system that uses water instead of organic solvent as solvent. In certain embodiments, the waterborne polyurethane coating liquid may include components such as oligomer polyols, chain extenders, diisocyanates and water. In certain embodiments, the oligomer polyol may include a mixture of one or more of polyether polyols and polyester polyols. For example, polylactic acid polyol, polycarbonate diol, polypropylene glycol, etc. In certain embodiments, the oligomer may be polylactic acid polyol and polycarbonate diol or a mixture thereof.

[0064] In some embodiments, the method for preparing the aqueous polyurethane coating solution may include the following steps:

[0065] (a) Acetone, isophorone diisocyanate (IPDI), polylactic acid polyol (PLA-OH Ma=2000), polycarbonate diol (PCDL Mn=1000), and 5% dibutyltin dilaurate (DBTDL) were added to a three-necked round-bottom flask equipped with a mechanical stirrer and a condenser and reacted at 80°C for 2 h;

[0066] (b) adding the chain extender dimethylaminopropylamine diisopropyl alcohol (DPA) and continuing the reaction for 3 h;

[0067] (c) then cooling to 65°C, adding hydroxyethyl acrylate (HEA) and a small amount of DBTDL and reacting for 4 hours;

[0068] (d) cooling the reaction system to 60° C. and adding methanol until the -NCO in the system is completely reacted;

[0069] (e) Deionized water was added to the flask, CO2 gas was introduced at 1000 rpm for 1 hour under high-speed stirring, and acetone was removed under vacuum for 1 hour to obtain a waterborne polyurethane coating solution.

[0070] In some embodiments, the preparation reaction of the waterborne polyurethane coating solution can be carried out under inert gas conditions.

[0071] In some embodiments, the preparation reaction of the waterborne polyurethane coating solution can be carried out in argon.

[0072] In some embodiments, the preparation reaction of the aqueous polyurethane coating solution can be carried out in N2.

[0073] The preparation method of the invisible braces provided in one of the embodiments of the present invention can carry out the surface grafting reaction of the antibacterial agent on the surface of the braces at room temperature, which only takes 1 hour, is time-saving, avoids high temperature, and will not affect the performance of the braces material.

[0074] The embodiments of this specification can play an antibacterial role by grafting quaternary ammonium salt antibacterial agents on the surface of invisible braces, and can also prevent enamel demineralization caused by plaque accumulation; the quaternary ammonium salt antibacterial agent is combined with the surface of the braces by the method of surface grafting, which can effectively solve the problems of easy shedding of the surface coating, unstable blending of antibacterial agents, and short maintenance time; adding a high elastic modulus water-based polyurethane coating to the edge of the braces can increase the pressure of the braces on the neck of the tooth, which helps to control the movement of the root, and adding periodontal drugs to the coating helps to control periodontitis; the edge of the braces contacts the edge of the gums, and can release drugs to the inflamed area, which is effective in anti-inflammatory; the braces coating is a water-based polyurethane component, which is skin-friendly and soft, and more comfortable to wear. The preparation method of the invisible braces provided in the embodiments of this specification can be carried out at room temperature, avoiding the influence of high temperature on the performance of the braces material, and the reaction time is short, and the preparation method is simple.

[0075] The present invention is described in detail below in conjunction with embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, some adjustments and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention. Example Example 1: Grafting DMADDM quaternary ammonium salt antibacterial agent on the inner surface of the braces

[0076] 1. Clean the braces: Use anhydrous ethanol for ultrasonic cleaning for 5 minutes, then use deionized water for ultrasonic cleaning for 5 minutes twice, and dry the braces at room temperature to constant weight.

[0077] 2. Prepare DMADDM grafting solution: weigh 2-5% of the weight of the braces anthraquinone and 2% of the weight of the braces DMADDM in anhydrous ethanol, and stir for 30 minutes using a magnetic stirring device.

[0078] 3. Soak the braces in DMADDM grafting solution for 30 minutes, and then use ultraviolet light to irradiate the side of the braces that contacts the teeth for 30 minutes while soaking in the grafting solution.

[0079] 4. Take the dental cap out of the grafting solution, use anhydrous ethanol and deionized water to alternately ultrasonically clean for 5 minutes for 3 times, and dry it at room temperature to constant weight. A dental cap with the function of preventing enamel demineralization is obtained. Figure 5 It is an infrared spectrum of a dental cap containing DMADDM quaternary ammonium salt antibacterial agent shown in some embodiments of this specification. Example 2: Adding a high elastic modulus waterborne polyurethane coating that releases Roflumilast to the braces

[0080] 1. Preparation of waterborne polyurethane coating liquid:

[0081] (1) Acetone, isophorone diisocyanate (IPDI), polylactic acid polyol (PLA-OH Ma=2000), polycarbonate diol (PCDL Mn=1000), and 5% dibutyltin dilaurate (DBTDL) were added to a 250 mL three-necked round-bottom flask equipped with a mechanical stirrer and a condenser, and the mixture was reacted at 80°C for 2 h. The chain extender dimethylaminopropylamine diisopropyl alcohol (DPA) was added and the reaction was continued for 3 h. The temperature was then lowered to 65°C, and hydroxyethyl acrylate (HEA) and a small amount of DBTDL were added and the reaction was continued for 4 h. The reaction system was cooled to 60°C, and methanol was added until the -NCO in the system was completely reacted. The entire reaction was carried out in N2.

[0082] (2) Deionized water was added to the flask, CO2 gas was introduced at 1000 rpm for 1 hour under high-speed stirring, and acetone was removed under vacuum for 1 hour to obtain a water-based polyurethane coating solution.

[0083] 2. Prepare the light-curable waterborne polyurethane containing drugs: dilute the prepared waterborne polyurethane with anhydrous ethanol to a polyurethane coating liquid with a content of 10%, add 5% of the total mass of the coating liquid as photoinitiator LAP and 20 μmol / ml of Roflumilast.

[0084] 3. Use a small brush to evenly apply the light-curing water-based polyurethane to the inner and outer surfaces of the formed braces. Use an ultraviolet lamp to irradiate the inner and outer surfaces at a distance of 10 cm for 30 minutes to form a water-based polyurethane coating that can release Roflumilast.

[0085] 4. Clean the appliance by ultrasonic cleaning with anhydrous ethanol for 5 minutes, then ultrasonic cleaning with deionized water for 5 minutes twice, and dry it at room temperature to constant weight. Example 3: Verification of the anti-inflammatory effect of invisible braces

[0086] 1. Preparation of light-curable waterborne polyurethane liquid

[0087] The aqueous polyurethane coating liquid is diluted with anhydrous ethanol to a polyurethane coating liquid with a content of 10%, and a photoinitiator LAP is added to account for 5% of the total mass of the aqueous polyurethane coating liquid, and mixed to obtain a light-curable aqueous polyurethane coating liquid.

[0088] 2. Preparation of invisible braces extracts containing different concentrations of Roflumilast

[0089] 0μmol / mL, 5μmol / mL, 10μmol / mL, and 20μmol / mL of Roflumilast were added to the light-curable water-based polyurethane liquid, which was applied to the surface of the invisible braces and light-cured, and then the invisible braces were used to prepare a 0.2g / mL extract.

[0090] 3. Verification of the anti-inflammatory effect of invisible braces using mouse macrophages

[0091] The above-mentioned invisible orthodontic appliance extract containing different concentrations of Roflumilast and the culture medium added with LPS inflammatory stimulating factor were used to culture mouse macrophage RAW264.7. After 12 hours of culture, PCR analysis of TNF-α inflammatory factors produced by mouse macrophages was performed. The results of PCR analysis are shown in Figure 6 .

[0092] like Figure 6 As shown, the expression of TNF-α in the group with LPS inflammatory stimulus was significantly increased compared with the group with 0μmol / ml Roflumilast extract. The other groups with Roflumilast significantly reduced the expression of TNF-α, among which the 20μmol / ml Roflumilast group was the most significant. The results show that the membrane with Roflumilast has a significant anti-inflammatory effect.

[0093] The basic concepts have been described above. Obviously, for those skilled in the art, the above detailed disclosure is only for example and does not constitute a limitation of this specification. Although not explicitly stated here, those skilled in the art may make various modifications, improvements and corrections to this specification. Such modifications, improvements and corrections are suggested in this specification, so such modifications, improvements and corrections still belong to the spirit and scope of the exemplary embodiments of this specification.

[0094] At the same time, this specification uses specific words to describe the embodiments of this specification. For example, "one embodiment", "an embodiment", and / or "some embodiments" refer to a certain feature, structure or characteristic related to at least one embodiment of this specification. Therefore, it should be emphasized and noted that "one embodiment" or "an embodiment" or "an alternative embodiment" mentioned twice or more in different positions in this specification does not necessarily refer to the same embodiment. In addition, certain features, structures or characteristics in one or more embodiments of this specification can be appropriately combined.

[0095] In addition, unless explicitly stated in the claims, the order of the processing elements and sequences described in this specification, the use of alphanumeric characters, or the use of other names are not intended to limit the order of the processes and methods of this specification. Although the above disclosure discusses some invention embodiments that are currently considered useful through various examples, it should be understood that such details are only for illustrative purposes, and the attached claims are not limited to the disclosed embodiments. On the contrary, the claims are intended to cover all modifications and equivalent combinations that are consistent with the essence and scope of the embodiments of this specification. For example, although the system components described above can be implemented by hardware devices, they can also be implemented only by software solutions, such as installing the described system on an existing server or mobile device.

[0096] Similarly, it should be noted that in order to simplify the description disclosed in this specification and thus help understand one or more embodiments of the invention, in the above description of the embodiments of this specification, multiple features are sometimes combined into one embodiment, figure or description thereof. However, this disclosure method does not mean that the features required by the subject matter of this specification are more than the features mentioned in the claims. In fact, the features of the embodiments are less than all the features of the single embodiment disclosed above.

[0097] In some embodiments, numbers describing the number of components and attributes are used. It should be understood that such numbers used in the description of the embodiments are modified by the modifiers "about", "approximately" or "substantially" in some examples. Unless otherwise specified, "about", "approximately" or "substantially" indicate that the numbers are allowed to vary by ±20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximate values, which may change according to the required features of individual embodiments. In some embodiments, the numerical parameters should take into account the specified significant digits and adopt the general method of retaining digits. Although the numerical domains and parameters used to confirm the breadth of their range in some embodiments of this specification are approximate values, in specific embodiments, the setting of such numerical values ​​is as accurate as possible within the feasible range.

[0098] Each patent, patent application, patent application publication, and other materials, such as articles, books, specifications, publications, documents, etc., cited in this specification are hereby incorporated by reference in their entirety. Except for application history documents that are inconsistent with or conflicting with the contents of this specification, documents that limit the broadest scope of the claims of this specification (currently or later attached to this specification) are also excluded. It should be noted that if the descriptions, definitions, and / or use of terms in the materials attached to this specification are inconsistent or conflicting with the contents described in this specification, the descriptions, definitions, and / or use of terms in this specification shall prevail.

[0099] Finally, it should be understood that the embodiments described in this specification are only used to illustrate the principles of the embodiments of this specification. Other variations may also fall within the scope of this specification. Therefore, as an example and not a limitation, alternative configurations of the embodiments of this specification may be considered consistent with the teachings of this specification. Accordingly, the embodiments of this specification are not limited to the embodiments explicitly introduced and described in this specification.

Claims

1. An invisible orthodontic appliance for treating periodontal disease and preventing enamel demineralization, characterized in that: The invisible braces include: A dental cap, a quaternary ammonium salt antibacterial agent, a remineralizer coating, and an aqueous polyurethane protrusion dot coating capable of releasing periodontal drugs; the periodontal drug is a PDE4 receptor inhibitor.

2. The invisible braces as described in claim 1, wherein the PDE4 receptor inhibitor is roflumilast, celecoxib, or apremilast.

3. The invisible braces according to any one of claims 1 to 2, wherein the quaternary ammonium salt antibacterial agent is grafted onto the surface of the braces in contact with the tooth surface; and the aqueous polyurethane protrusion dot-shaped coating capable of releasing periodontal drugs is on the inner side of the braces in contact with the tooth.

4. A method for preparing an invisible orthodontic appliance for treating periodontal disease and preventing enamel demineralization, the method comprising: S1, using the membrane to make the braces; S2, photopolymerizing and grafting the quaternary ammonium salt antibacterial agent on the inner surface of the braces at room temperature to obtain a braces containing the quaternary ammonium salt antibacterial agent; S3. The inner side of the dental cap containing the quaternary ammonium salt antibacterial agent obtained in step S2 is attached to the tooth, and a water-based polyurethane protrusion dot coating that can release a PDE4 receptor inhibitor is added to obtain the invisible braces for treating periodontal disease and preventing enamel demineralization.

5. The preparation method according to claim 4, wherein the membrane for making the braces is a multilayer structure of at least two layers, wherein the layer of material closest to the tooth surface is thermoplastic polyurethane (TPU), and the remaining layers can be any material selected from polyethylene terephthalate-1,4-cyclohexanedimethanol ester (PETG), thermoplastic polyurethane (TPU), polycarbonate (PC), polyethylene terephthalate (PET), ethylene-vinyl acetate copolymer (EVA), and polyamide (PA).

6. The preparation method according to claim 4, wherein the remineralizing agent is blended with the TPU material to produce the diaphragm.

7. The preparation method according to any one of claims 4 to 6, wherein the multilayer film of the dental brace is manufactured by a co-extrusion method, comprising: The scanned model of the subject's oral cavity is collected, and a tooth model is 3D printed after computer design. A vacuum laminator is used to heat the film until it softens and then vacuum-adsorbed onto the tooth model. The shape of the gum edge is then cut by laser cutting or manual trimming to produce the braces.

8. The preparation method according to claim 4, wherein the photopolymerized grafted quaternary ammonium salt antibacterial agent comprises: The dental cap was immersed in a quaternary ammonium salt antibacterial agent grafting solution for 30 minutes, and ultraviolet light was used to irradiate the dental cap contacting the tooth side for 30 minutes.

9. preparation method as claimed in claim 8, described quaternary ammonium salt antibacterial agent grafting liquid preparation method comprises: Weigh 2-5% of the weight of the brace with anthraquinone and 2% of the weight of the brace with a quaternary ammonium salt antibacterial agent in anhydrous ethanol, and stir for 30 minutes using a magnetic stirring device to obtain the quaternary ammonium salt antibacterial agent grafting liquid.

10. The preparation method according to claim 4, wherein the protruding dot-shaped coating comprises: Light-curable waterborne polyurethane containing PDE4 receptor inhibitor; The method for preparing the photocurable waterborne polyurethane containing a PDE4 receptor inhibitor comprises: The aqueous polyurethane coating liquid is diluted with anhydrous ethanol to a polyurethane coating liquid with a content of 10%, and 5% of the total mass of the aqueous polyurethane coating liquid is added with a photoinitiator LAP and 20 μmol / ml of a PDE4 receptor inhibitor to obtain the photocurable aqueous polyurethane containing the PDE4 receptor inhibitor.

11. The preparation method according to claim 10, wherein the preparation method of the aqueous polyurethane coating liquid comprises: (a) Acetone, isophorone diisocyanate (IPDI), polylactic acid polyol (PLA-OH Ma=2000), polycarbonate diol (PCDL Mn=1000), and 5% dibutyltin dilaurate (DBTDL) were added to a three-necked round-bottom flask equipped with a mechanical stirrer and a condenser and reacted at 80°C for 2 h; (b) adding the chain extender dimethylaminopropylamine diisopropyl alcohol (DPA) and continuing the reaction for 3 h; (c) then cooling to 65° C., adding hydroxyethyl acrylate (HEA) and a small amount of DBTDL, and reacting for 4 hours; (d) cooling the reaction system to 60° C. and adding methanol until the -NCO in the system is completely reacted; (e) Deionized water was added to the flask, CO2 gas was introduced at 1000 rpm for 1 hour under high-speed stirring, and acetone was removed under vacuum for 1 hour to obtain the waterborne polyurethane coating solution.

12. The preparation method according to claim 11, wherein the preparation reaction of the aqueous polyurethane coating liquid is carried out in N2.

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