Orthodontic adhesives and methods of using the same

Abstract

To provide, among others, orthodontic adhesives, orthodontic adhesive systems, and methods of using the adhesives and adhesive systems, which do not require complex pre-attachment treatment and which reduce issues associated with debonding orthodontic devices from teeth.SOLUTION: An orthodontic adhesive (10) includes components capable of allowing easy debonding of an orthodontic device (12) from a patient's tooth (14). The adhesive includes an engineered marine mussel protein. The adhesive (10) may include at least one photocleavable moiety. The adhesive (10) is applied to one or more individual layers. One of the components of the adhesive (10) is capable of binding to a tooth, and the other component may be capable of binding to the orthodontic device (12). A method of bonding an orthodontic device (12) to a tooth (14) includes applying a layer of an orthodontic adhesive (10) to either the tooth (14) or the orthodontic device (12) or to the tooth (14) and orthodontic device (12), and affixing the orthodontic device (12) to the tooth with the orthodontic adhesive (10) situated between the tooth (14) and the orthodontic device (12). The engineered marine mussel protein includes one or more catechol moieties or one or more derivatives of a catechol moiety.SELECTED DRAWING: None

Description

[Technical field]

[0001] Field The present invention relates generally to the field of orthodontic adhesives, adhesive systems, and methods of using those adhesives. [Background technology]

[0002] background Conventional orthodontic treatments involving orthodontic brackets or other devices that can be attached to a patient's teeth may require preparation of the enamel before attaching the device to the tooth. Preparation of the tooth surface may be by a series of steps including cleaning, acid etching, sealing, and intermediate rinsing and drying steps before the clinician applies an adhesive. For example, to bond brackets to tooth enamel, each tooth is first cleaned with an abrasive slurry, such as pumice powder, to remove a thin film from the enamel. The cleaned surface is then rinsed and dried, after which a phosphoric acid etchant is carefully placed on the tooth surface at the location where the clinician wishes to attach the orthodontic device. The acid etching step demineralizes the enamel surface and removes approximately 30 μm of hydroxyapatite from the enamel rods. After an etching time of 30 to 90 seconds, the etchant is washed away with a water spray and high-flow aspirator. Thus, the etching step results in a porous structure.

[0003] Following the drying step after the etching step, a sealant (e.g., Ortho Solo™ sealant) is applied to the etched surface. The sealant is allowed to penetrate the porous, acid-etched surface. When the sealant hardens, a mechanical interlock is created between the tooth and the sealant. An adhesive (e.g., Enlight) and bracket can be pressed onto the sealed surface with the adhesive between the bracket and the sealant. The adhesive can be a composite resin paste adhesive that includes a mixture of methacrylate monomers, photoinitiators, and glass / hydroxyapatite powders. When the adhesive hardens, the bracket is firmly fixed to the sealant. This bonding arrangement results in a sandwich-like structure of the sealant and adhesive sandwiched between the tooth surface and the orthodontic bracket. This procedure and bonding arrangement is repeated for each tooth that will receive an orthodontic device, as well as orthodontic brackets and molar tubes, which may include 28 teeth per patient.

[0004] Traditional preparation methods have many drawbacks. From the clinician's perspective, it is a manual and very time-consuming process. It is not surprising that the working hours during the entire bonding procedure are long. Overall, bonding orthodontic brackets to teeth is expensive. From the patient's perspective, the process is uncomfortable and enamel removal is often irreversible due to the difficulty of remineralizing the dental hard tissue. Thus, the tooth surface may be permanently damaged by acid etching. Some patients may have an allergic reaction to the etchant. Liquid etchants may run to the gums where they may irritate the soft tissue. Gel etchants can be placed more precisely but require skilled application and are more difficult to remove. In either application, if the etchant must be washed off, care must be taken not to splash or wash the etchant in a way that harms the patient or clinician, but the washing process should be thorough so that the etching reaction is complete and there is no residual acid or mineral debris that would interfere with the mechanical interlocking between the tooth and the device.

[0005] During treatment, demineralization of the enamel surfaces adjacent to the fixed appliances spreads. The demineralization presents as white spot lesions (WSLs). If left untreated, WSLs can progress to cause caries cavities and can also result in aesthetic problems. Therefore, prevention, diagnosis, and treatment of WSLs is important to minimize caries and tooth discoloration that can mar the aesthetics of a patient's smile. However, the problems and costs do not end with bonding.

[0006] After orthodontic treatment is completed, the clinician must remove the orthodontic brackets from each tooth. This debonding method requires the clinician to break the bonds that were formed during the bonding process. Mechanically fracturing the bonds can require significant skill on the part of the clinician if the patient is trying to avoid pain. Even orthodontic brackets that include design features for easier debonding can leave a significant adhesive / sealant residue on the tooth surface after the bracket is removed. This residue must be removed mechanically with a dental bur, a process that is very uncomfortable for the patient and tedious for the clinician. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] US Patent Publication No. 2016 / 0160097 [Patent Document 2] US Patent Publication No. 2017 / 0217999 [Non-patent literature]

[0008] [Non-Patent Document 1] Shafiq et al., "Bioinspired Underwater Bonding and Debonding on Demand," 51 Angew. Chem. Int. Ed. 4332-35 (2012) Summary of the Invention [Problem to be solved by the invention]

[0009] Thus, there is a need for orthodontic adhesives, orthodontic adhesive systems, and methods of using the adhesives and adhesive systems that do not require the complex pre-attachment procedures discussed above and that reduce the problems associated with debonding orthodontic devices from teeth. [Means for solving the problem]

[0010] SUMMARY OF THE PRESENT APPLICATION The present invention overcomes the above-mentioned and other shortcomings and drawbacks of previously known orthodontic adhesives. While the present invention will be described in connection with certain embodiments, it is to be understood that the invention is not limited to these embodiments. Rather, the present invention includes all alternatives, modifications, and equivalents that may be included within the spirit and scope of the present invention.

[0011] In one embodiment, the orthodontic adhesive comprises an engineered marine mussel protein. The engineered marine mussel protein comprises at least one catechol or catechol-like moiety.

[0012] In one embodiment, the adhesive further comprises a nitrocatechol derivative. In one embodiment, the nitrocatechol derivative is nitrodopamine. In one embodiment, the nitrocatechol derivative is nitronorepinephrine. In one embodiment, the nitrocatechol derivative is nitroepinephrine.

[0013] In one embodiment, the modified marine mussel protein comprises catechol-methacrylate.

[0014] In one embodiment, the orthodontic adhesive comprises a photocleavable bis-methacrylate.

[0015] In another aspect of the invention, a method of adhering an orthodontic device to a tooth comprises applying a layer of an orthodontic adhesive to the tooth and / or the orthodontic device. The orthodontic adhesive comprises a modified marine mussel protein. The method further comprises affixing the orthodontic device to the tooth with the orthodontic adhesive located between the tooth and the orthodontic device.

[0016] In one embodiment, the modified marine mussel protein comprises a catechol moiety or one or more derivatives of a catechol moiety and the step of applying a layer comprises a catechol moiety or one or more derivatives of a catechol moiety to the tooth.

[0017] In one embodiment, the catechol moiety comprises catechol-methacrylate.

[0018] In one embodiment, the method further comprises applying an acrylate moiety and / or a methacrylate moiety to the layer. In one embodiment, the moiety is a bis-methacrylate.

[0019] In another aspect of the invention, attachments for use with aligners during orthodontic treatment comprise modified marine mussel proteins.

[0020] In another aspect of the invention, a kit comprises an orthodontic device and a modified marine mussel protein.

[0021] BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the detailed description set forth below, serve to explain the principles of the invention. [Brief description of the drawings]

[0022] [Figure 1] FIG. 1 illustrates a set of orthodontic brackets, including individual brackets, attached to a patient's teeth. [Diagram 2] FIG. 2 is a cross-sectional view taken along the line 2-2 in FIG. [Diagram 3] FIG. 3 is an enlarged view of the enclosed area 3 of FIG. 2 according to one embodiment of the present invention. [Figure 4] FIG. 3 is an enlarged view of the enclosed area 3 of FIG. 2 according to one embodiment of the present invention. [Diagram 5] FIG. 3 is an enlarged view of the enclosed area 3 of FIG. 2 according to one embodiment of the present invention. [Figure 6] FIG. 3 is an enlarged view of the enclosed area 3 of FIG. 2 according to one embodiment of the present invention. [Figure 7] Figure 7A shows an exemplary wettable adhesive group according to one embodiment of the present invention. Figure 7B shows an enlarged schematic diagram of the enclosed area 3 of Figure 2 according to one embodiment of the present invention. Figure 7C shows an exemplary monomer comprising a polymerizable group according to one embodiment of the present invention. [Figure 8A] FIG. 1 illustrates photocleavage of an exemplary monomer according to one embodiment of the present invention. [Figure 8B] FIG. 1 illustrates cross-linking and photocleavage of exemplary monomers according to one embodiment of the present invention. [Figure 9] FIG. 1 is a perspective view of one embodiment of the present invention including an attachment of one embodiment of the present invention attached to a patient's teeth to facilitate orthodontic treatment with aligners. [Figure 10] 10 is a cross-sectional view of the aligner and teeth shown in FIG. 9 taken through one of the attachments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Detailed Description In this detailed description, all references to the Periodic Table of the Elements refer to the copyrighted Periodic Table of the Elements published in 2001 by CRC Press, Inc., and any reference to one or more groups refers to one or more groups as set forth in the Periodic Table of the Elements using the IUPAC system of numbering groups. As used herein, the term "(poly)" refers to one or more, or in other words, one or more, as the case may be.

[0024] To address these and other issues, in one embodiment, a clinician can use an orthodontic adhesive system 10 to bond an orthodontic device to a patient's teeth. As described in detail below, the orthodontic adhesive system 10 includes a modified protein. By way of example only, as shown in FIG. 1, orthodontic brackets 12 can be used in an orthodontic procedure. One orthodontic bracket 12 can be affixed to each of a plurality of teeth 14 with the orthodontic adhesive system 10. The orthodontic bracket 12 defines a substantially transversely disposed archwire slot 16 that receives an archwire 20. The orthodontic bracket 12 can be bonded and secured to an exterior facing surface 22 with the orthodontic adhesive system 10. Although not shown in FIG. 1, the orthodontic adhesive system 10 can be between each of the orthodontic brackets 12 and the corresponding teeth 14. Although brackets 12 are shown and described herein, other orthodontic appliances can be bonded to the patient's teeth using embodiments of the present invention. For example, the orthodontic adhesive system 10 can be used to bond lingual retainers and bite turbos, to name a few, to the patient's teeth.

[0025] With reference to Figures 2-6, the orthodontic adhesive system 10 may include a single layer 18 of one or more components as shown in Figure 6, or multiple layers 24 of individual, separately applied components as shown in Figures 3-5. Although multiple layers 24 are illustrated in the same portion of Figures 3-5, this is not necessary for the present invention. In accordance with the present invention, the multiple layers 24 of individual, separately applied components may differ in size and thickness relative to one another. The layers 18, 24 include one or more components configured to bond to either the tooth surface 22 or the orthodontic appliance 12, or one or more components configured to form a bond between other components in a sandwich-like composite structure. When attached to the respective teeth 14 using the orthodontic adhesive system 10, the brackets 12 and archwires 20 together provide an orthodontic treatment.

[0026] According to embodiments of the present invention, the orthodontic adhesive system 10 may eliminate one or more of the tooth preparation steps described above. For example, the orthodontic adhesive system 10 may not require one or more of the cleaning and acid etching steps described above, while still securely securing the orthodontic bracket 12 to the corresponding tooth 14. Additionally, the orthodontic adhesive system 10 may improve the ease with which the orthodontic bracket 12 may be intentionally removed from the tooth 14. Thus, with the orthodontic adhesive system 10 of embodiments of the present invention, no significant mechanical force is required to debond the bracket 12 from the tooth 14, and the patient may not experience discomfort during removal.

[0027] After removal of the orthodontic bracket 12, the adhesive residue, if any, on the tooth 14 will be minimized. Thus, embodiments of the present invention will also eliminate or minimize the step of cleaning the tooth 14 after removal. As another benefit to the patient, the orthodontic adhesive system 10 will eliminate or minimize the demineralization problem caused by acid etching during preparation of the tooth surface. The orthodontic adhesive system 10 of embodiments of the present invention can have self-repairing properties, such that the orthodontic adhesive system 10 resists aging and long-term degradation. As another benefit to both the patient and the clinician, the system 10 allows for reversible bonding and debonding of the device 12 to the tooth 14. That is, the bonding network of the orthodontic adhesive system 10 can be selectively activated to bond and deactivated to debond with the surface of the tooth 14 or from the orthodontic device 12. The clinician can easily correct the placement of a misplaced device.

[0028] A complicating factor for orthodontic adhesives is the environment they are exposed to. The patient's mouth is filled with saliva, an aqueous solution of electrolytes, enzymes, and cellular material. This environment requires the complex tooth preparation and bonding methods described above to create a mechanical bond between the teeth and the orthodontic device.

[0029] Applicants have determined that the oral environment is similar to seawater, which is a solution of water, electrolytes, and biological materials. In the ocean, mussels have an extraordinary ability to attach and detach themselves to submerged surfaces. According to Applicants, the use of modified marine mussel proteins, or similar proteins as components of the orthodontic adhesive system 10, provides sufficient bond strength between the orthodontic device, e.g., orthodontic bracket 12, and tooth 14. The bonding process can be accomplished without the complex preparation and bonding methods described above. An embodiment of the orthodontic adhesive system 10 includes selected modified mussel proteins, or similar components that mimic the attachment and / or detachment functions of the mussel in the oral environment. The modified mussel proteins are synthetically produced.

[0030] Marine mussels secrete a glue-like adhesive substance known as byssus, which is important for strong adhesion to rocks and other surfaces in turbulent marine environments. The byssus is a bundle of thread-like material that radiates outward. It is composed of four parts: the attachment disk, the thread, the stem, and the base. Mussel byssus is protein-like in nature. In other words, mussel byssus is a protein derived from marine mussels. The byssus is attached to the base of the mussel axon, which controls its tension through a combination of 12 contractile muscles. More than 25 different mussel axon proteins (mfp) have been identified in the byssus, of which five (mfp-2 to mfp-6) are unique to the attachment disk. These five mfps generally contain a high content of the rare modified amino acid 3,4-dihydroxy-L-phenylalanine (hereafter "DOPA") (1).

[0031] [ka]

[0032] DOPA contains a catechol moiety, as shown in (1) above. When combined with oxidant cations from seawater under basic pH conditions, quinine is produced by oxidation of the catechol moiety of DOPA. Quinine can form a cross-linked polymer matrix with a network of bonds. Furthermore, when bound to rocks, the catechol moiety of DOPA can undergo chelation with inorganic oxides found in rocks. Intermolecular aggregation of DOPA can occur with the addition of multivalent cations, e.g., Fe. 3+ ions and Ca 2+ The adhesion of the mussel to various substrates, such as wood, metal, and mineral surfaces, is facilitated by the cations. These cations form metal complexes between the unoxidized catechols of DOPA, facilitating wet adhesion of the bond network in seawater. It has been found that it is the catechol functional group of DOPA that allows it to attach to external surfaces during the adhesion process and at least facilitates adhesion of the mussel to various substrates, such as wood, metal, and mineral surfaces, especially when submerged in seawater. An embodiment of the orthodontic adhesive system 10 includes selected modified marine mussel proteins or similar components that mimic the attachment and / or detachment functions of the mussel in the oral environment. Exemplary adhesives include those disclosed in U.S. Patent Publication No. 2016 / 0160097 and U.S. Patent Publication No. 2017 / 0217999, each of which is incorporated herein by reference in its entirety. The modified marine mussel proteins may be synthetic or genetically modified.

[0033] With reference to FIG. 7A, in one exemplary embodiment, the modified marine mussel protein of the orthodontic adhesive system 10 includes monomers having catechol and / or catechol-like moieties, and thus has properties similar to DOPA shown in (1). The catechol and / or catechol-like moieties of the orthodontic adhesive system 10 include nitrocatechol-containing compounds or one or more nitrocatechol derivative-containing compounds, which provide functional groups for chelation, self-polymerization, and crosslinking. As a further example, FIG. 7A shows an exemplary catechol-like-containing compound having a wet adhesive group that bonds to enamel. The wet adhesive group includes one or more functional monomers (FIG. 7C) that crosslink with other components of the adhesive system 10. The functional monomer includes at least one of a phosphonate moiety and a cyclic disulfide moiety, both of which can undergo reaction with the polymerizable group of the monomer.

[0034] 2-6, the catechol-like moiety and functional monomer of the modified protein adhesive of the orthodontic adhesive system 10 can be joined together to form at least a portion of layer 18, layer 24, with the catechol-like moiety bonded to the tooth surface 22. This portion can facilitate adhesion of the monomer to the tooth surface 22 without first cleaning, etching, and drying the tooth surface 22. By eliminating one or more of these preparation steps, embodiments of the invention reduce procedure time. The reduction in time to bond a bracket to a tooth can be reduced by approximately 80%. For example, traditional preparation and bonding can require as much as four minutes per tooth. Embodiments of the invention can reduce this to approximately 30 seconds per tooth. A typical bonding appointment requires 2-3 hours of patient commitment. Embodiments of the invention significantly reduce the time required for bonding and are advantageous for at least that reason. For example, according to embodiments of the invention, a clinician may bond orthodontic appliances to a patient's teeth on the same day as the initial appointment. This is not commonly done due to the extensive office-time requirements associated with bonding the appliances to the patient's teeth. Additionally, reduced bonding time, and the associated reduced office-time, will reduce costs for the clinician, but also potentially increase profitability by increasing the clinician's capacity to see more patients.

[0035] In any of the exemplary systems 10 shown in Figures 3-6, monomers of the engineered protein adhesive adhere to tooth surface 22 and form a base to which the orthodontic device is ultimately attached. For example, with reference to Figure 3, in one embodiment, orthodontic adhesive system 10 can include four layers that together form composite layer 24. In that regard, orthodontic adhesive system 10 can include one or more separately applied layers 26, 28, 30, and 32 that together bond orthodontic bracket 12 to tooth 14. Each of the components in layers 26, 28, 30, and 32 bond with the components of the other layers and / or with tooth 14 or orthodontic bracket 12.

[0036] In an exemplary embodiment, layer 26 is in direct contact with tooth surface 22. Layer 26 includes modified mussel protein monomers having catechol-like moieties as described above. By way of example, the modified mussel protein monomers include catechol methacrylate. Unlike some conventional orthodontic sealants, the catechol-like moieties form an adhesive network through hydrogen bonding and metal-ligand complexes with hydroxyapatite without the need for one or more preparatory steps such as cleaning, etching, or drying. Additionally, the catechol-like moieties can undergo Michael addition with enamel or dentin collagen to chemically bond layer 26 to tooth surface 22.

[0037] 3, by way of example only, layer 26 may be on the order of about 100 nanometers thick. Layer 26 may be thicker or thinner than 100 nanometers, depending on the application technique and viscosity of layer 26. Layer 26 may be very thin relative to the overall thickness of the joint formed by adhesive system 10 between bracket body 12 and tooth 14. Layers 28, 30, and 32 may be applied separately, with the monomer of layer 26 adhered to tooth surface 22.

[0038] Layer 28 can directly contact and chemically bond to the catechol-like containing monomers forming layer 26 before or after the layer has cured. In the embodiment shown in FIG. 3, layer 28 can include nitrocatechol-containing and nitrocatechol derivative-containing compounds (described below) that bond to the dried monomers forming layer 26. In an exemplary embodiment, layer 28 is modified when exposed to a particular wavelength of light. Thus, at the end of treatment, the clinician can expose system 10 to the light to modify layer 28. As a result, the layer dissolves and releases orthodontic bracket 12. The clinician then easily removes orthodontic bracket 12.

[0039] In one embodiment, with reference to Figure 3, the encapsulant can form layer 30. Layer 30 can be in direct contact with and chemically bonded to the nitrocatechol-containing and nitrocatechol derivative-containing compounds forming layer 28, either before or after the layers are cured. In the embodiment shown in Figure 3, layer 30 can be an acrylate-based resin encapsulant that bonds to layer 28. In one embodiment, the encapsulant forming layer 30 is a commercially available orthodontic encapsulant, such as Ortho Solo™ available from Kerr Corporation of Orange, CA.

[0040] As shown, layer 32 can be applied directly to layer 30 in a separate application. Layer 32 chemically bonds to layer 30 and mechanically bonds to orthodontic bracket 12. By way of example only, layer 32 can include a resin, such as a methacrylate resin, that can include acrylate and / or methacrylate moieties that chemically bond with the acrylate-based resin encapsulant of layer 30 when exposed to light of a preselected wavelength. When applied, layer 32 can include a photoinitiator that facilitates curing of layer 32. In one embodiment, the resin is a commercially available orthodontic adhesive, such as Grenggloo® or Blugloo, each available from Ormco Corporation of Orange, Calif.

[0041] In the case of layer 32, which may include a photoinitiator, orthodontic bracket 12 may be pressed against composite layers 26, 28, 30, and 32, as shown in FIG. 3. Adhesive layer 32 may be cured by exposing it to light, for example, visible blue light (e.g., wavelengths of about 450 nm to about 475 nm). This photocuring method cures at least layer 32. As a further example, each of layers 26, 28, 30, and 32 may be cured at the same time or at different times. The timing of each cure is determined by the clinician's preference. A clinician may prefer to partially cure layer 26 to make it more tacky, and then apply the remaining layers while finally curing each of layers 26, 28, 30, and 32 together. When layers 26, 28, 30, and 32 are cured, orthodontic adhesive system 10 bonds orthodontic bracket 12 to tooth surface 22.

[0042] In the exemplary orthodontic adhesive system 10 shown in Figures 4, 5, and 6, the above functional groups for layers 26, 28, 30, and 32 can be combined with fewer than four layers. For example, the functional groups of layers 28 and 30 can be combined to provide a three-layer system (Figure 4). As a further example, a two-layer system (Figure 5) can combine the functional groups of the catechol-like portion of layer 26 with the sealant in layer 30, which can include nitrocatechol-containing compounds and nitrocatechol derivative-containing compounds, as previously described. In this case, the functional groups of layers 26, 28, and 30 of Figure 3 are present in layer 40 of Figure 5. Thus, with reference to Figure 5, layer 40 is applied to tooth surface 22. The catechol-like portion of layer 40 can form an adhesive network with the enamel of surface 22 by hydrogen bonding and metal-ligand complexing without the need for one or more of washing, etching, or drying steps.

[0043] With respect to Figure 5, layer 42 may be the same as layer 32 of Figure 3. In particular, layer 42 may include a resin, such as a methacrylate resin, and may include acrylate and / or methacrylate moieties that chemically bond with the resin of layer 40. The bond network may be diagrammed in Figure 7B, discussed above.

[0044] In FIG. 6, in one embodiment, the orthodontic adhesive system 10 includes a single layer 18 having components that combine the functionality of layers 26, 28, 30, and 32 described above. By way of example, the catechol-like portion of layer 18 can form an adhesive network with enamel through hydrogen bonding and metal-ligand complexes without the need for one or more of cleaning, etching, or drying the tooth surface 22. Additionally, layer 18 can include a debonding compound and a resin, e.g., a methacrylic resin, that can include acrylate and / or methacrylate moieties that chemically bond to the acrylate resin sealant, ultimately forming a bond between the orthodontic adhesive system 10 and the bracket 12. The figure is not drawn to scale. Thus, although layers 26, 28, 30, and 32 of Figure 3, layers 26, 30, and 32 of Figure 4, layers 40 and 42 of Figure 4, and layer 18 of Figure 5 are depicted with approximately the same uniform thickness, embodiments of the invention are not limited to the relative thickness ratios depicted, and the thickness of each layer can vary independently of the other layers.

[0045] An exemplary system, orthodontic adhesive system 10, is diagrammed in Figure 7B, in which a catechol-like containing layer 26 adheres to hydroxyapatite or calcium ions in the enamel or dentin at surface 22. The monomers of layer 26 can bond to the tooth surface 22 and crosslink to the sealant of layer 30 (Figure 4). The methacrylate of layer 32 crosslinks to the surface of bracket 12. The areas where crosslinking occurs may be shown as crosslinked polymer brushes at 36.

[0046] In an exemplary embodiment, with reference to Figures 8A and 8B, the nitrocatechol-containing and nitrocatechol derivative-containing compounds are polymerized with a biologically acceptable polymer, e.g., PEG-N. D4 The nitrocatechol-containing compound and the nitrocatechol derivative-containing compound can be attached as an end group to a four-arm star-shaped poly(ethylene glycol), known as . The nitrocatechol-containing compound and the nitrocatechol derivative-containing compound can then be attached, for example, to a tooth surface 22 or to a separately applied layer of a monomer having a catechol-like moiety (e.g., layer 26 in FIG. 3). As with the catechol moiety of DOPA described above, the nitrocatechol-containing compound and the nitrocatechol derivative-containing compound can undergo oxidation to form a crosslinked network, or metal chelation between the non-oxidized nitrocatechol and its derivative to form a strong bond between two or more nitrocatechol-containing compounds. Exemplary nitrocatechol derivative-containing compounds include nitrocatechol, nitrodopamine, nitronorepinephrine, and nitroepinephrine, among others. Some of these compounds not only mimic the adhesive properties of DOPA to wet surfaces, but the catechol-like moiety, for example, the nitrocatechol-containing compound or one or more nitrocatechol derivative-containing compounds, can be photocleavable.

[0047] In that regard, the photocleavable moiety can interact with a wavelength of light ("hv" in FIG. 8). As shown in FIG. 8A, in one embodiment, a monomer containing a catechol-like moiety can be cleaved when exposed to a wavelength of light, thereby facilitating at least a partial depolymerization of the orthodontic adhesive system 10. An exemplary photocleavable moiety includes a photocleavable bis-methacrylate. Photocleavage of the monomer can be effected by one or more additional moieties that are pendant to one or more of the nitrocatechol-containing and derivative-containing compounds described above.

[0048] In one exemplary embodiment, with reference to FIG. 8B, the bond between the leaving group X and the ethyl group pendant to the nitrocatechol moiety can be cleaved with a photon of light having a predetermined energy. By way of example, the photocleavable moiety of the orthodontic adhesive system 10 can be any moiety that can be broken when exposed to light in the infrared (IR) spectrum (i.e., wavelengths from about 700 nm to about 1 mm). Thus, for example, exposure to IR light can depolymerize the orthodontic adhesive system 10 and promote debonding of the bracket 12 from the tooth surface 22. IR light is believed to be advantageous because it passes through both hard (e.g., teeth) and soft (e.g., lips, cheeks, and tongue) surfaces. A clinician can more easily expose the orthodontic adhesive system 10 to IR light to debond the bracket 12 from the tooth 14. Alternatively, the photocleavable moiety can be broken when exposed to light in the ultraviolet (UV) spectrum (i.e., wavelengths from about 10 nm to about 400 nm). Exemplary photocleavable moieties include those reported in Shafiq et al., “Bioinspired Underwater Bonding and Debonding on Demand,” 51 Angew. Chem. Int. Ed. 4332-35 (2012) (hereinafter “Shafiq”), which is incorporated by reference in its entirety.

[0049] In one embodiment, the bond between the nitrocatechol derivative moiety and the biologically acceptable polymer can be cleaved upon exposure to light. In this manner, the orthodontic adhesive system 10 can be debonded via light exposure. As an example, layer 30 of FIG. 4 can include a photocleavable moiety. In that regard, the bond between the nitrocatechol derivative-containing compound and the biologically acceptable polymer can be weakened or broken by exposing the bond to IR light. As an example, a typical orthodontic bracket can be bonded to a tooth and can achieve a shear strength of 10 MPa to 20 MPa. Exposure to IR or UV light can reduce the shear strength to 1 MPa or less. As a result, the nitrocatechol derivative can remain attached to the surface, but the biologically acceptable polymer is detached from the nitrocatechol derivative moiety. When applied to the embodiment of FIG. 4, for example, when exposed to IR light, layer 30 can be denatured, in which case layer 30 can be broken, such that bracket 12 and layer 32 are detached from tooth 14. After debonding, layer 26 can remain on tooth surface 22. Thus, the dental brackets can be firmly adhered to the patient's teeth during treatment, if necessary, but can also be easily removed from the teeth by exposing the adhesive to an IR light source when treatment is completed or the device needs to be repositioned or replaced.

[0050] Once the treatment is complete, in one embodiment, the debonding step can include exposing the adhesive to IR light. The orthodontic bracket 12 will either fall off or require only a small amount of force to remove. Any force applied in combination with light exposure is believed to be substantially less than the traditional force required to debond an orthodontic device from a tooth. In addition to reducing the bond force, the debonding step can minimize or eliminate the need to scrape off the remaining adhesive when the orthodontic device is removed. In the case of traditional adhesives that require mechanical removal (i.e., scraping off), patient discomfort from mechanical removal is eliminated by using the adhesive of the present invention. Additionally, the adhesive of the present invention tends to provide stronger cohesive strength, thus minimizing emergency appointments. For example, bond strength according to embodiments of the present invention can reach approximately 15 MPa or more, minimizing accidental debonding. This bond strength is achieved while also reducing the time it takes to intentionally debond an orthodontic device.

[0051] In one embodiment of the present invention, the clinician can remove multiple brackets 12, even an entire arch of brackets 12, by using the archwire 16 at the same time. The clinician can expose the orthodontic adhesive system 10 to IR light. Once at least a portion of the orthodontic adhesive system 10 has been modified, the clinician can pull the archwire 16 while still engaging each bracket 12 to the arch. The brackets 12 become detached, although still connected to the archwire 16. In this manner, the clinician can remove each of the brackets 12 with a single pull on the archwire 16. In this manner, it is possible to leave no residual adhesive on the teeth 14. As another advantage, this prevents accidental loss or ingestion of individual brackets, which can significantly reduce office hours, e.g., by more than 90%.

[0052] Further, according to an embodiment of the present invention, the photocleavable moiety allows for reversible adhesion of the orthodontic adhesive system 10 to the tooth surface 22. The reversible adhesive bonding method may be of the fast-curing variety (e.g., with the catechol derivative-containing compound present on the tooth and the functional monomer present on the restoration, curing can occur in a matter of seconds when the orthodontic device is pressed against the tooth). The adhesion may be reversible in the sense that it can be bonded and then debonded at least twice. This may be useful if the orthodontic bracket 12 is initially placed improperly. The orthodontic bracket 12 can then be debonded, repositioned, and then rebonded to the tooth surface 22. In one embodiment, the adhesive's adhesive properties can be activated and deactivated during bonding and debonding, respectively. Thus, the adhesive may facilitate on-demand bonding and debonding methods that allow for easy repositioning of the orthodontic device. This may be referred to as a reusable adhesive system. Advantageously, orthodontic device placement can be foolproof since the adhesive can be selectively bonded, debonded, and then rebonded without the addition of additional adhesive, without the fear of the adhesive polymerizing prior to proper placement. Clinically, repositioning methods are common and cumbersome, therefore, the adhesive embodiments described herein save time on repositioning, representing a significant change in the standard of patient care.

[0053] In one embodiment of the present invention, the orthodontic adhesive may be used in a kit. The kit may include an orthodontic device, such as orthodontic brackets 12, with the orthodontic adhesive pre-applied. The kit may include bubble wrap to individually organize the brackets 12. The clinician may individually remove the orthodontic brackets 12 from the packaging and press them against the patient's teeth in a particular order. The clinician may then cure the pre-applied adhesive using light, such as blue light.

[0054] 9 and 10, in one embodiment, the orthodontic adhesive system 10 can be used with other orthodontic appliances, such as aligners 60. The aligners 60 can be configured to fit and interact with one or more attachments 62 bonded to one or more teeth 14. Each attachment 62 can be a predetermined shaped configuration of the orthodontic adhesive system 10. That is, the orthodontic adhesive system 10 can be formed into rectangular, square, circular, oval, or triangular shaped attachments bonded to a tooth surface, similar to that described above with respect to the orthodontic bracket 12 (FIG. 1). The attachments 62 can be formed entirely of the adhesive system 10.

[0055] The aligners 60 may be configured with corresponding bulges 64 that engage the attachments 62 during orthodontic treatment. Advantageously, each of the attachments 62 may be easily bonded to the tooth surface prior to treatment with the aligners 60, and easily debonded by exposing it to a particular wavelength of light. The attachments 62 may be applied to the teeth using a template (not shown), which allows the clinician to more easily position the attachments 62 on the patient's teeth. Once correctly positioned, the attachments 62 may interact with the corresponding bulges 64 of the aligners 60.

[0056] In order to facilitate a more complete understanding of embodiments of the present invention, the following non-limiting examples are provided. EXAMPLES

[0057] Example 1 A primer solution of 7.5% by weight 10-methacryloxydecyl dihydrogen phosphate (MDP) modified to have a lower acid number (i.e., purified to remove HCl by-product), 0.005% by weight catechol-methacrylate (CMA) (using eugenol as the backbone of the CMA), and 0.0075% by weight butylated hydroxytoluene (BHT), balance acetone, was applied with a brush to bovine teeth that had been prepared by wiping with a tissue. No other preparation techniques were used to prepare the tooth surface.

[0058] A second solution of 10% by weight photocleavable bis-methacrylate, 0.01% by weight N,N-di-methyl-amino-ethyl methacrylate (DMAEMA), 0.01% by weight camphoroquinone (CQ), and 0.001% by weight BHT, with the balance being acetone, was applied with a brush to the dried primer, which forms a debonding layer.

[0059] Ortho Solo® encapsulant was applied to the debonding layer.

[0060] The Grengloo® adhesive is placed on the orthodontic bracket and then pressed against the debonding layer with the adhesive in contact with the debonding layer.

[0061] The layer was then exposed to a broad spectrum curing light for a few seconds (on the order of about 5 seconds). Total preparation and bonding time was about 1 minute per sample.

[0062] The bond strength measured for multiple samples was between 17 MPa and 19 MPa.

[0063] The wire shear bond strengths for sample size 30 ranged from a high of 36.3 MPa to a low of 17.4 MPa. To demonstrate debonding, a first set of the 30 samples collected above was exposed to UV light for 10 seconds. After exposure, the wire shear bond strengths ranged from a high of 15.6 MPa to a low of 12.7 MPa. A second set of the 30 samples collected above was exposed to UV light for 30 seconds. After exposure, the wire shear bond strengths ranged from a high of 9.5 MPa to a low of 0.

[0064] (Comparative Example) For comparison with Example 1, orthodontic brackets were bonded to bovine teeth using commercially available adhesives. Manufacturer's instructions for bonding of all commercially available adhesives were followed. Standard tooth preparation techniques prior to bonding of the brackets to each tooth included, in order, cleaning the teeth with pumice powder, rinsing with water, air drying, and application of an etchant.

[0065] Two groups of 30 specimens each were prepared using Orthosolo® and Grengroo® and Transbond™ XT primer and Transbond™ XT adhesive, respectively, commercially available from 3M Company.

[0066] Another group of 30 samples of self-etching Transbond™ Plus primer (L-pop delivery) and Transbond™ XT adhesive was also prepared.

[0067] Respective wire shear bond tests showed the following results compared to the experimental samples of Example 1:

[0068] [Table 1]

[0069] The present invention has been described by the description of various preferred embodiments, and while these embodiments have been described in a certain degree of detail, it is not the intention of the inventors to restrict or in any way limit the scope of the appended claims to such details. Further advantages and modifications will be readily apparent to those skilled in the art. The various features of the present invention may be used alone or in any combination, depending on the needs and preferences of the user. [Explanation of symbols]

[0070] 10 Orthodontic adhesive system 12 Orthodontic brackets 14 teeth 16 Archwire slot 18 Single Layer 20 Archwire 22 Tooth Surface 24 composite layer 26 composite layer 28 composite layer 30 composite layers 32 Composite layer 60 Aligners 62 Attachment 64 Bulge

Claims

1. 1. An orthodontic adhesive system for use in a method of adhering an orthodontic device to a tooth, the method comprising: applying a layer of an orthodontic adhesive system to tooth surfaces and / or to the orthodontic device, the orthodontic adhesive system comprising: A modified marine mussel protein comprising at least one catechol or catechol derivative moiety; and A nitrocatechol derivative selected from the group consisting of nitrodopamine, nitronorepinephrine, and nitroepinephrine. A process comprising: affixing the orthodontic device to a surface of the tooth with the orthodontic adhesive system positioned between the tooth and the orthodontic device. Including, The tooth surface is moistened. system.

2. The system of claim 1 , wherein the catechol moiety comprises catechol-methacrylate.

3. applying acrylate and / or methacrylate moieties to said layer 2. The system of claim 1 further comprising:

4. The system of claim 3, wherein the moiety is a bis-methacrylate.

5. 10. The system of claim 1, wherein the orthodontic adhesive system further comprises a sealant.

6. 10. The system of claim 1, wherein the step of attaching the orthodontic device to the tooth surface comprises curing the orthodontic adhesive system with light.

7. 10. The system of claim 1, wherein the orthodontic adhesive system exhibits a shear bond strength of 10 MPa to 20 MPa after the orthodontic adhesive system is applied to the tooth surface.

8. 10. The system of claim 1, wherein in the step of applying the orthodontic adhesive system to the tooth surface, the tooth surface is not treated with any composition prior to the step of applying the orthodontic adhesive system to the tooth surface.

9. 1. An orthodontic adhesive system for use in a method of adhering an orthodontic device to a tooth, the method comprising: applying a layer of an orthodontic adhesive system to tooth surfaces and / or to the orthodontic device, the orthodontic adhesive system comprising: A modified marine mussel protein comprising at least one catechol or catechol derivative moiety; and A nitrocatechol derivative selected from the group consisting of nitrodopamine, nitronorepinephrine, and nitroepinephrine. A process comprising: affixing the orthodontic device to a surface of the tooth with the orthodontic adhesive system positioned between the tooth and the orthodontic device. Including, applying the layer of the orthodontic adhesive system to the tooth surfaces and / or the orthodontic device is performed without applying an acid etching solution to the tooth surfaces prior to applying the layer of the orthodontic adhesive system to the tooth surfaces and / or the orthodontic device. system.

10. The system of claim 9, wherein the catechol moiety comprises catechol-methacrylate.

11. applying acrylate and / or methacrylate moieties to said layer 10. The system of claim 9 further comprising:

12. The system of claim 11, wherein the moiety is a bis-methacrylate.

13. 10. The system of claim 9, wherein the orthodontic adhesive system further comprises a sealant.

14. 10. The system of claim 9, wherein the step of affixing the orthodontic device to the tooth surface comprises curing the orthodontic adhesive system with light.

15. 10. The system of claim 9, wherein the orthodontic adhesive system exhibits a shear bond strength of 10 MPa to 20 MPa after the orthodontic adhesive system is applied to the tooth surface.

16. 10. The system of claim 9, wherein in the step of applying the orthodontic adhesive system to the tooth surface, the tooth surface is not treated with any composition prior to the step of applying the orthodontic adhesive system to the tooth surface.

Images