Peri-implantitis treatment device and method for regulating biofilm activity

Abstract

The peri-implantitis treatment device (1) according to the present invention is provided with: an electrode (14) for applying a negative potential to a metal part (7) of a dental implant (8); a potential controller for controlling the potential of the electrode (14); and a mouthpiece (2) that holds the electrode (14) and the potential controller and is attached to the dental implant (8). The peri-implantitis treatment device (1) according to the present invention can effectively inactivate even bacteria (bacterial colonies) that are in a deep periodontal pocket hardly cleaned mechanically and in a state of forming a biofilm against which antibiotics are less effective.

Description

[Technical Field]

[0001] The present invention relates to a peri-implantitis treatment device and a method for regulating biofilm activity. [Background technology]

[0002] It is known that bacteria can invade the gap between the dental implant and the gums, causing the probing pocket depth (PPD) to deepen, resulting in a condition called peri-implantitis. If peri-implantitis develops, depending on the depth of the PPD, various treatments are attempted, such as mechanical cleaning using the device described in Patent Document 1, cleaning with an antibacterial agent, and local or systemic drug therapy with an antibacterial agent. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2017-532175 Summary of the Invention [Problem to be solved by the invention]

[0004] Even if peri-implantitis develops and treatment with mechanical cleaning and antibacterial agents is attempted, bacterial infection often ultimately leads to alveolar bone loss, necessitating surgical removal of the dental implant.

[0005] There are generally two reasons why surgical removal of an implant is chosen. One is that although mechanical cleaning deep into the periodontal pocket is thought to be effective in preventing and slowing the progression of peri-implantitis, mechanical cleaning becomes more difficult as the PPD deepens. In other words, as the PPD deepens, it becomes more difficult to remove the causative bacteria around the implant, making treatment more difficult and ultimately forcing the implant to be removed.

[0006] Another reason is that the causative bacteria form biofilms, which are difficult to clean with antibacterial agents and disinfect, making mechanical cleaning and drug therapy difficult.

[0007] Considering the characteristics of peri-implantitis, which become more difficult to treat due to the nature of the PPD becoming deeper, the present invention aims to provide a peri-implantitis treatment device that can effectively inactivate bacteria (groups) even in deep periodontal pockets where mechanical cleaning is difficult and which have formed biofilms that are resistant to antibiotics. Another object of the present invention is to provide a method for regulating biofilm activity that can be applied to research on bacteria (groups) in a biofilm-forming state. [Means for solving the problem]

[0008] As a result of extensive research into achieving the above object, the present inventors have found that the above object can be achieved by the following configuration.

[0009] [1] A peri-implantitis treatment device comprising: an electrode for applying a negative potential to the metal portion of a dental implant; a potential control device for controlling the potential of the electrode; and a mouthpiece that holds the electrode and the potential control device and is attached to the dental implant. [2] The peri-implantitis treatment device according to [1], wherein the potential control device controls the potential of the electrode to exceed the lower limit of the potential window and to be less than −0.4 V based on a silver / silver chloride electrode. [3] The current density of the electrode is 1.0 μA / cm 2 The peri-implantitis treatment device according to [1] or [2], wherein the peri-implantitis treatment device is less than 100%. [4] A method for adjusting biofilm activity, comprising applying a potential exceeding the lower limit of the potential window and less than -0.4 V versus a silver / silver chloride electrode to a conductor on which a biofilm has formed, thereby inactivating the biofilm. [5] A method for regulating the activity of a biofilm described in [4], which comprises bringing the conductor into direct contact with a bacterial suspension and applying a positive potential to the conductor to form the biofilm. [6] A method for adjusting biofilm activity described in [4] or [5], wherein the inactivation is carried out in a liquid medium, and further includes comparing the OD values ​​of the liquid medium before and after the inactivation, and providing information for determining the degree of progress of the inactivation based on an increase in the OD value. [7] The current density of the above conductor is 1.0 μA / cm 2 The method for regulating biofilm activity according to any one of [4] to [6], wherein the biofilm activity is less than 100%. [8] The method for adjusting the activity of a biofilm according to any one of [4] to [7], wherein the biofilm is formed by oral bacteria. [Effects of the Invention]

[0010] According to the present invention, a peri-implantitis treatment device can be provided that can effectively inactivate bacteria (groups) even in deep periodontal pockets where mechanical cleaning is difficult and in a state where bacteria have formed biofilms that are resistant to antibiotics. Furthermore, the present invention can provide a method for regulating biofilm activity that can be applied to research on bacteria (groups) in a biofilm-forming state.

[0011] The peri-implantitis treatment device of the present invention (hereinafter also referred to as "the device") comprises an electrode for applying a negative potential to the metal part of a dental implant, a potential control device for controlling the potential of the electrode, and a mouthpiece that holds the electrode and the potential control device and is attached to the dental implant.

[0012] This device has an electrode for applying a negative potential to the metal part of the dental implant. As will be shown in the examples below, according to the research of the inventors, it is presumed that the causative bacteria of peri-implantitis adhere to the metal part of the dental implant in the periodontal pocket of the dental implant, form a biofilm, and become pathogenic in the anaerobic environment of the biofilm.

[0013] In this case, it is presumed that the causative bacteria use the metal part of the dental implant as an acceptor (electron acceptor) for electrons released during the metabolism of electron sources (e.g., organic compounds).

[0014] The device of the present invention applies a negative potential to the metal part of the dental implant, thereby inhibiting the transfer of electrons to the metal part and inhibiting the metabolism of the causative bacteria(s), thereby reducing (inactivating) their activity. Furthermore, since the electron transfer occurs between the biofilm, which is in direct contact with the metal part of the dental implant, and the metal part, the effect is direct and extremely advantageous compared to drug therapy using antibacterial agents, the effectiveness of which is reduced by the biofilm.

[0015] Furthermore, when the potential control device of this device controls the electrode potential to be below -0.4 (vs. Ag / AgCl) V, exceeding the lower limit of the potential window, a better inactivation effect can be obtained. First, when the electrode potential (i.e., the potential of the metal part of the dental implant) is controlled to a potential exceeding the lower limit of the potential window, the generation of hydrogen is more suppressed. This allows the electrons (e - ) can be more easily transferred from the electrode to the causative bacteria(s), further improving the inactivation effect.

[0016] Furthermore, by controlling the electrode potential to less than -0.4 (vs Ag / AgCl) V, the causative bacteria (groups) find it more difficult to transfer electrons to the electrode, which suppresses the metabolism of electron sources (organic compounds, etc.), resulting in a more effective inactivation effect.

[0017] In addition, the current density is 0.1 μA / cm 2 If the current density is less than 0.1 nA / cm, the burden on the living body is likely to be smaller even when the device is attached to the living body. Although there is no particular lower limit for the current density, from the viewpoint of obtaining a better inactivation effect, a current density of 0.1 nA / cm is preferred. 2 The above is preferable.

[0018] The method for adjusting biofilm activity of the present invention (hereinafter also referred to as "the method") involves inactivating the biofilm by applying a potential that is greater than the lower limit of the potential window and less than -0.4 (vs Ag / AgCl) V to a conductor on which a biofilm has formed.

[0019] When a potential exceeding the lower limit of the potential window is applied to a conductor on which a biofilm has formed, hydrogen generation is further suppressed. - ) becomes more easily transferred from the conductor to the causative bacteria(s), resulting in the inactivation of the biofilm. Furthermore, by applying a potential of less than -0.4 (vs Ag / AgCl) V to the conductor, the bacteria (groups) find it more difficult to transfer electrons to the conductor, resulting in a better activity regulation effect.

[0020] Furthermore, if this method involves directly contacting a conductor with a bacterial suspension and applying a positive potential to the conductor to form a biofilm, it can be used to study the formation and disappearance of biofilms by specific bacteria, as well as drugs that promote or inhibit this.

[0021] Furthermore, when inactivation by this method is carried out in a liquid medium and further includes comparing the OD values ​​of the liquid medium before and after inactivation and providing information for determining the degree of inactivation progress based on an increase in the OD value, the progress of inactivation can be more easily managed without having to check the state of the biofilm by microscopic observation, etc.

[0022] In addition, the current density in this method is 0.1 μA / cm 2 If the current density is less than 0.1 nA / cm, the influence on the living body can be reduced when the conductor is an implant or the like that is placed in the living body. Although there is no particular lower limit for the current density, from the viewpoint of obtaining a better inactivation effect, a current density of 0.1 nA / cm is preferred. 2 The above is preferable.

[0023] Furthermore, when the biofilm in this method is formed by oral bacteria, this method can be easily applied to the development of a method for preventing peri-implantitis. [Brief explanation of the drawings]

[0024] [Figure 1] 1 is a perspective view illustrating an example of a peri-implantitis treatment device according to an embodiment of the present invention. [Figure 2] FIG. 1 is a schematic cross-sectional view of a peri-implantitis treatment device 1 attached to a first premolar of the mandible. [Figure 3] 1 is a hardware configuration diagram of a peri-implantitis treatment device 1. FIG. [Figure 4] FIG. 1 is a functional block diagram of a peri-implantitis treatment device 1. [Figure 5] FIG. 2 is a flow diagram according to an embodiment of the method. [Figure 6] 1 is a scanning electron microscope image of a biofilm formed on an electrode. [Figure 7] FIG. 1 is a partially enlarged view of a scanning electron microscope image of a biofilm formed on an electrode. [Figure 8] This is the measurement result of the current value. [Figure 9] This is a scanning electron microscope image of the electrode surface 15 hours after the start of application of a potential (-400 mV). [Figure 10] FIG. 10 is a partially enlarged view of FIG. [Figure 11] This is a scanning electron microscope image of the electrode surface 15 hours after the start of application of a potential (-600 mV). [Figure 12] FIG. 12 is a partially enlarged view of FIG. [Figure 13] This is a scanning electron microscope image of the electrode surface 15 hours after the start of application of a potential (-800 mV). [Figure 14] FIG. 14 is a partially enlarged view of FIG. DETAILED DESCRIPTION OF THE INVENTION

[0025] The present invention will be described in detail below. The following description of the components may be based on a representative embodiment of the present invention, but the present invention is not limited to such an embodiment. In this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​before and after "to" as the lower and upper limits.

[0026] [Peri-implantitis treatment device] A peri-implantitis treatment device according to an embodiment of the present invention will be described with reference to the drawings.

[0027] Fig. 1 is a perspective view showing an example of a peri-implantitis treatment device according to an embodiment of the present invention. In Fig. 1, the peri-implantitis treatment device 1 is composed of a band-shaped mouthpiece 2 that covers from the crown of a first premolar 4 on the left side of the mandible fitted with an implant prosthesis to the periodontal tissue 5, and a substrate housing section 3 that houses a substrate having each of the hardware components described below.

[0028] Although the peri-implantitis treatment device 1 is configured to cover one prosthetic tooth, the peri-implantitis treatment device of the present invention is not limited to the above and may be configured to cover multiple prosthetic teeth or multiple teeth other than the prosthetic tooth (i.e., healthy teeth).Furthermore, it may be configured to cover all the teeth in the mandible or maxilla.

[0029] 2 is a schematic cross-sectional view of the peri-implantitis treatment device 1 attached to a mandibular first premolar. The peri-implantitis treatment device 1 has a mouthpiece 2 arranged to cover a dental implant 8 consisting of a crown portion 6 and a metal portion 7 made up of an implant body and an abutment, and a substrate receiving portion 3 arranged on the mouthpiece 2.

[0030] A substrate 10 on which each piece of hardware described below is mounted is disposed within the substrate housing portion 3. Electrodes 14 consisting of a working electrode 11, a counter electrode 12, and a reference electrode 13 are connected to the substrate 10. The working electrode 11 is in direct contact with the metal part 7 of the dental implant 8, and the counter electrode 12 and the reference electrode 13 are in direct contact with the periodontal tissue 5.

[0031] 3 is a hardware configuration diagram of the peri-implantitis treatment device 1. The peri-implantitis treatment device 1 includes a processor 21, a storage device 22, a communication interface (I / F) 23, a potential control device 24 connected to the electrodes 14, and a power supply 25. Each component is connected to each other via a bus 26 so as to be able to communicate with each other, and is mounted on a substrate 10.

[0032] The processor 21 controls each part of the peri-implantitis treatment device 1 to realize its functions. The processor 21 may be, for example, a microprocessor, a processor core, a multiprocessor, an application-specific integrated circuit (ASIC), a field programmable gate array (FPGA), or a general-purpose computing platform (GPGPU). graphics processing units), etc.

[0033] The storage device 22 has the function of temporarily and / or non-temporarily storing various programs and data, and provides a working area for the processor 21. The storage device 22 is, for example, a ROM (Read Only Memory), a RAM (Random Access Memory), an HDD (Hard Disk Drive), a flash memory, or an SSD (Solid State Drive).

[0034] The potential control device 24 controls the potential of the electrode 14 and measures the current value. Specifically, a negative potential is applied to the metal portion 7 of the dental implant 8, and the current value is measured. The potential control device 24 is typically a potentiostat and is built into the substrate 10.

[0035] The electrodes 14 consist of a working electrode 11 for applying a negative potential to the metal part 7 of the dental implant 8, a counter electrode 12 and a reference electrode 13. Of the electrodes 14, the working electrode 11 is in direct contact with the metal portion 7 of the dental implant 8. Generally, the metal portion 7 of the dental implant 8 is composed of a root portion (implant body) and an abutment portion (abutment), and is made of titanium alloy, pure titanium, Co-Cr-Mo alloy, etc. Meanwhile, the counter electrode 12 and the reference electrode 13 are in contact with the periodontal tissue 5. There are no particular limitations on the materials for the working electrode 11 and the counter electrode 12, and any known electrode material may be used. The reference electrode 13 is a silver / silver chloride electrode, but other known reference electrodes may also be used.

[0036] The working electrode 11 must be in contact with the metal part 7 of the dental implant 8, but the counter electrode 12 and the reference electrode 13 may be in contact with any part of the oral cavity, and may be in contact with the periodontal tissue 5 as shown in Figure 2, or may be in contact with the mucous membrane inside the cheek, the mucous membrane under the tongue, or the mucous membrane between the left and right upper gums.

[0037] The power supply 25 supplies the power necessary to drive each part of the peri-implantitis treatment device 1. The power supply 25 is typically an all-solid-state battery, and is surface-mounted on the substrate 10. This all-solid-state battery can be charged, for example, by a wireless charging system described in JP 2020-191772 A or the like. The power supply 25 is not limited to an all-solid-state battery, but may be any other conventionally known battery (for example, a lithium ion battery), and may not be surface-mounted on the substrate 10.

[0038] The communication interface (I / F) 23 performs communication for inputting operating conditions of the potential control device 24 from outside, and for outputting the potential of the working electrode 11 controlled by the potential control device 24 and the current value measured by the potential control device 24 to outside. The peri-implantitis treatment device 1 has a processor 21, a memory device 22, a communication interface 23, and a potential control device 24, but the peri-implantitis treatment device of the present invention is not limited to the above and may have a microcomputer that combines some or all of the functions of each of the above parts.

[0039] The mouthpiece 2 holds the substrate 10 provided with the above-mentioned components in the substrate housing portion 3, and is attached to the crown portion 6 with the working electrode 11 in direct contact with the metal portion 7. The space inside the substrate accommodating portion 3 may be sealed with a sealing material.

[0040] 4 is a functional block diagram of the peri-implantitis treatment device 1. The peri-implantitis treatment device 1 is made up of a control unit 30, a communication unit 31, a potential control unit 32, and a storage unit 33.

[0041] The control unit 30 includes a processor 21 and controls the communication unit 31, the potential control unit 32, and the storage unit 33 to realize the functions of the peri-implantitis treatment device 1.

[0042] The storage unit 33 is configured to include the storage device 22. The storage unit 33 has the function of reading out programs necessary for controlling each unit as needed, storing information (potential, current value) acquired by the potential control device 24, and reading out this information in response to a request from the control unit 30.

[0043] The communication unit 31 includes a communication interface 23, and is a function realized when a program stored in the storage device 22 is executed by the processor 21 and the communication interface 23 is controlled. The communication unit 31 has the function of accepting external input of the operating conditions of the potential control device 24 (such as the potential to be applied and the time for applying the potential), transmitting data such as current values ​​acquired by the potential control device 24 to the outside, and transmitting logs related to the operation of the device to the outside.

[0044] The potential control unit 32 is configured to include a potential control device 24 and an electrode 14 connected to it, and is a function realized by the processor 21 executing a program stored in the memory device 22 and controlling the potential control device 24. The potential control unit 32 has a function of applying a negative potential to the metal portion 7 of the dental implant 8 via the working electrode 11 that is in contact with the metal portion 7, and measuring the current value.

[0045] When treating peri-implantitis using the peri-implantitis treatment device 1, first, the mouthpiece 2 is attached to the dental implant 8 so that the working electrode 11 comes into contact with the metal portion 7 of the dental implant 8 to be treated. Next, the potential of the electrode 14 is controlled by the potential control unit 32 according to the conditions pre-stored in the memory unit 33 or the conditions input from the outside via the communication unit 31, and a negative potential is applied to the metal part 7 of the dental implant 8.

[0046] The applied potential is preferably above the lower limit of the potential window and less than −0.4 (vs Ag / AgCl) V. The time for applying the potential varies depending on factors such as the progress of peri-implantitis and may be adjusted as appropriate, but is generally preferably 1 to 24 hours. For example, by wearing the peri-implantitis treatment device 1 while sleeping and operating it for about 5 to 10 hours, the biofilm in the periodontal pocket can be sufficiently inactivated, and by repeating this process, the progression of peri-implantitis can be suppressed and treated.

[0047] [Method for adjusting biofilm activity] Next, the method of the present invention will be described. The method of the present invention is a method for regulating biofilm activity, which comprises applying a potential exceeding the lower limit of the potential window and less than −0.4 (vs. Ag / AgCl) V to a conductor on which a biofilm has formed, to inactivate the biofilm.

[0048] Conductors on which biofilms have formed include, for example, medical instruments that are placed in the body, including dental implants, examination instruments such as endoscopes, and metal parts of medical instruments used in surgical operations. By applying this method to such conductors, it is possible to inactivate biofilms in the complex shapes and in the fine details that are difficult to reach by mechanical cleaning, thereby suppressing bacterial infection and allowing the conductors to be used in a cleaner state.

[0049] The conductor on which the biofilm is formed may be an electrode used in a laboratory. For example, if microorganisms are cultured on a transparent electrode to form a biofilm and then inactivated by this method, the morphology during the inactivation process can be observed and changes in the current obtained during the inactivation process can be used for research.

[0050] FIG. 5 is a flow diagram according to an embodiment of the method. First, a positive potential is applied to a conductor in a liquid medium, and a biofilm is formed on the conductor (step S10). The liquid medium contains a group of bacteria capable of forming a biofilm and water, and may also contain electrolytes, electron sources (organic compounds), and the like in addition to the above. The potential is not particularly limited, but a potential below the upper limit of the potential window is preferred. In the method according to the embodiment of the present invention, a conductor on which a biofilm has already formed may be used, in which case step S10 can be omitted.

[0051] Next, the OD (optical density) value of the liquid medium is measured (step S11). The OD value correlates with the amount of suspended bacterial population in the liquid medium. The liquid medium may be replaced with a new liquid medium after the biofilm has formed. When the liquid medium is replaced after the biofilm has formed, it is preferable that the replaced liquid medium does not contain bacteria. Using a liquid medium that does not contain bacteria can provide more accurate information for evaluating the progress of biofilm inactivation when a negative potential is applied to the conductor.

[0052] Next, a potential exceeding the lower limit of the potential window and less than −0.4 V (vs. Ag / AgCl) is applied to the conductor (step S12). There are no particular limitations on the method of applying the potential. For example, the conductor on which the biofilm has formed may be used as a working electrode, and a counter electrode and a reference electrode may be brought into contact with a liquid medium, and these may be controlled by a potentiostat.

[0053] The time for applying the potential is not particularly limited and may be appropriately selected depending on the purpose, for example, 1 to 24 hours.

[0054] Next, the OD value of the liquid medium is measured (step S13). When the biofilm is inactivated by applying a potential, the bacteria in the biofilm are suspended in the liquid medium. Therefore, the OD value changes before and after the application of a negative potential. This change in OD value can be used as an indicator of inactivation.

[0055] If the OD value increases due to the application of the potential (step S14: YES), it is highly likely that inactivation has progressed and bacteria have been released into the liquid medium. In this case, information for determining whether inactivation is progressing is provided (step S15).

[0056] Examples of this information include the difference (increase) in the OD value before and after application of a negative potential, the magnitude of the OD value after application of a negative potential, and the increase in the OD value per unit time. [Example]

[0057] Below, we will explain the results of experiments to demonstrate the mechanism of treatment for peri-implantitis using this device. Note that the following experimental data is for illustrative purposes only and is not intended to limit the operating conditions of this device.

[0058] The experiment was carried out using a three-electrode electrochemical cell with an ITO (Indium Tin Oxide) electrode as the working electrode, a platinum electrode as the counter electrode, and a silver / silver chloride electrode as the reference electrode, under anaerobic conditions with nitrogen bubbling. First, a liquid medium (defined media) containing 10 mM lactate as an electron source was added to the cell, and Streptococcus mutans (OD 0.1) was inoculated. The cells were then cultured at 37°C for 24 hours with the working electrode potential set to +0.2 V (200 mV, vs. Ag / AgCl) to form a biofilm.

[0059] Figure 6 is a scanning electron microscope image of a biofilm formed on an electrode, and Figure 7 is a partially enlarged view of the image. In both images, a thick bacterial aggregate (biofilm) can be seen formed on the electrode.

[0060] Next, the liquid medium was removed, and a new liquid medium (sterile) was added, and the OD value (562 nm) at this time was measured. Next, the potential of the working electrode was controlled to -400 mV, -600 mV, and -800 mV, respectively, and the current value and OD values ​​were measured after 2 hours and 16 hours. Figure 8 shows the current measurement results, and Table 1 shows the OD measurement results. Note that the lower limit of the potential window in this experimental system was experimentally confirmed to be approximately -1.0 V (vs. Ag / AgCl), and -800 mV is a potential that exceeds this lower limit.

[0061] [Table 1]

[0062] The results in Table 1 confirm that, at all potentials, the OD value after 2 hours had increased compared to when the potential was applied, and had increased sufficiently after 16 hours.

[0063] 9 to 14 are scanning electron microscope images of the electrode surface 15 hours after the start of potential application: Fig. 9 is at -400 mV, Fig. 10 is a partially enlarged view, Fig. 11 is at -600 mV, Fig. 12 is an enlarged view, Fig. 13 is at -800 mV, Fig. 14 is an enlarged view.

[0064] In both cases, comparison with FIG. 6 confirmed that the bacterial colonies on the electrodes were destroyed, that is, the biofilms were inactivated. [Industrial Applicability]

[0065] The peri-implantitis treatment device of the present invention can effectively inactivate bacterial groups even in deep periodontal pockets where mechanical cleaning is difficult and which have formed biofilms that are resistant to antibiotics. The peri-implantitis treatment device of the present invention is also believed to be effective in preventing peri-implantitis, and if dental implant users use it regularly, it will also lead to a reduction in medical costs.

Claims

1. A method for regulating biofilm activity (excluding methods for treating humans), comprising applying a potential exceeding the lower limit of the potential window and less than −0.4 V versus a silver / silver chloride electrode to a conductor on which a biofilm has formed, thereby inactivating the biofilm.

2. 2. The method for modulating biofilm activity according to claim 1, comprising bringing the conductor into direct contact with a bacterial suspension and applying a positive potential to the conductor to form the biofilm.

3. the inactivation is carried out in a liquid medium; The method for adjusting biofilm activity described in claim 1 further comprises comparing the OD values ​​of the liquid medium before and after the inactivation, and providing information for determining the degree of progress of the inactivation based on the increase in the OD value.

4. The current density of the conductor is 1.0 μA / cm ２ The method for regulating biofilm activity according to any one of claims 1 to 3, wherein the biofilm activity is less than 100%.

5. The method for regulating biofilm activity according to any one of claims 1 to 3, wherein the biofilm is formed by oral bacteria.

6. A peri-implantitis treatment device for inactivating a biofilm formed on a metal part of a dental implant by the method for adjusting biofilm activity according to claim 1, an electrode for applying a negative potential to the metal part of the dental implant; a potential control device for controlling the potential of the electrode; a mouthpiece that holds the electrodes and the potential control device and is attached to the dental implant; The potential control device controls the potential of the electrode to exceed the lower limit of the potential window and to be less than −0.4 V relative to a silver / silver chloride electrode.

7. The current density of the electrode is 1.0 μA / cm ２ The peri-implantitis treatment device according to claim 6, wherein the thickness is less than 1 mm.

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