JP7092484B2 - Osteoblast colonization treatment device on metal material embedded in body bone. - Google Patents

Description

The present invention relates to an osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material, and is particularly suitable for improving osteoblast colonization and proliferation on an in-vivo bone-implanted metal material. It relates to an osteoblast colonization processing device.

Conventionally, examples of the metal material for implanting bone in the body include implants used for dental treatment. Not limited to implants, members that are embedded in the body and come into contact with bone are integrated with the body only after the bone has settled on the surface of the member, and treatment is completed. However, it takes a certain period of time for the bone to settle in the member embedded in the body, and it has been required to shorten this period.

For example, in dental implants, a technique capable of promoting the proliferation of osteoblasts by pre-treating the bone-embedded portion of the implant has been published (Patent Document 1).

In this method, UV is applied to the bone-embedded portion of the implant in advance to treat the surface so as to have a positive charge, and then the implant is implanted (Patent Document 2).

Japanese Unexamined Patent Publication No. 2008-80102 Special Table 2012-509750 Gazette

In the above Patent Document 1, since ultraviolet rays are irradiated for 1 to 2 hours, the patient must be sitting on a treatment table or the like during that time, which is practical as a treatment device for a patient who has undergone implant (internal bone implant metal material) treatment. There is a problem that it is not the target.
In Patent Document 2, osteoblasts based on modification of the surface of the implant (internal bone-embedded metal material) only by irradiating the titanium oxide implant with ultraviolet rays containing a wavelength of about 170 nm to about 270 nm before the treatment. Although it was aimed at promoting the proliferation of bones, it was not considered to irradiate with ultraviolet rays while wearing it on the human body.
In the present invention, hydrogen peroxide, which is harmless even in the human body after implanting, is supplied to the implant implanting portion, and UV irradiation is performed here by scattering and condensing, and hydroxylation is performed on the surface of the metal material embedded in the bone in the body. It is an object of the present invention to provide an osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material that generates radicals to efficiently treat the surface of an implant member and improve osteoblast colonization and proliferation.

In order to solve the above problems, the present invention provides the following osteoblast colonization treatment apparatus on a bone-implanted metal material in the body. That is, as the first invention, it is a treatment device for improving the colonization and proliferation of osteoblasts in a metal material embedded in a bone in the body, and has a hydrogen peroxide solution discharge port for discharging hydrogen peroxide solution and hydrogen peroxide. Implantation of bone in the body equipped with an ultraviolet irradiation port that irradiates hydrogen hydrogen water supplied from a water discharge port with one or more of ultraviolet rays, near-ultraviolet rays, and blue visible light (hereinafter referred to as "ultraviolet rays, etc."). A device for colonizing osteoblasts on a metallic material (corresponding to claim 1).

The body according to claim 1, wherein in addition to the above-mentioned features, the hydrogen peroxide solution discharge port and the ultraviolet ray irradiation port are chip shapes that can be inserted into the gap formed between the embedded metal material embedded in the body and the bone. Osteoblast colonization treatment device on bone-implanted metal material (corresponding to claim 2).

In addition to the above-mentioned features, the osteoblast colonization treatment apparatus on the bone-implanted metal material in the body according to claim 1 or 2, wherein the irradiation port for ultraviolet rays or the like is configured to scatter ultraviolet rays or the like (corresponding to claim 3). ..

The osteoblast colonization treatment apparatus (claimed) on a metal material embedded in a bone in the body according to any one of claims 1 to 3, wherein the irradiation port for ultraviolet rays and the like is configured to collect ultraviolet rays and the like in addition to the above-mentioned features. Corresponding to item 4).

The osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material according to any one of claims 1 to 4, wherein the discharge rate of the discharged hydrogen peroxide solution is 100 CC / min or less in addition to the above-mentioned features. (Corresponding to claim 5).

The osteoblast colonization treatment on an in-vivo bone-implanted metal material according to any one of claims 1 to 5, wherein the amount of ultraviolet rays or near-ultraviolet rays irradiated in addition to the above-mentioned features is 0.1 milliwatt or more. Device (corresponding to claim 6).

According to claim 1, in addition to the above-mentioned characteristics, the concentration of the hydrogen peroxide is 1 w / v% or more and 7 w / v% or less, and the concentration of the hydrogen peroxide stabilizer is 81 ppm (mg / L) or less in this aqueous solution. Item 3. The apparatus for colonizing osteoblasts on a metal material implanted in a bone in the body according to any one of Item 6 (corresponding to claim 7).

The seventh aspect of claim 7, wherein in addition to the above-mentioned characteristics, the concentration of the hydrogen peroxide is 1 w / v% or more and 7 w / v% or less, and the concentration of the hydrogen peroxide stabilizer is 0 ppm (mg / L) in this aqueous solution. An osteoblast colonization treatment device on a metal material embedded in a bone (corresponding to claim 8).

The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to claim 7 or 8, wherein the concentration of hydrogen peroxide is 2 w / v% or more and 6 w / v% or less in addition to the above-mentioned characteristics (corresponding to claim 9). ).

The osteoblast colonization treatment apparatus on a metal material embedded in a bone according to claim 7 or 9, wherein the hydrogen peroxide stabilizer is one or more of phenacetin and acetanilide in addition to the above-mentioned characteristics (corresponding to claim 10). ..

The osteoblast colonization on the bone-implanted metal material in the body according to any one of claims 7 to 10, wherein in addition to the above-mentioned characteristics, the impurity heavy metal content is only 0.001 w / v% or less with respect to hydrogen peroxide. Processing device (corresponding to claim 11).

As a second invention, a hydrogen peroxide solution is supplied to a metal material for bone implantation in the body, and at the same time, one or more of ultraviolet rays, near-ultraviolet rays, and blue visible light (hereinafter referred to as "ultraviolet rays, etc.") is irradiated to the bone in the body. A method for colonizing osteoblasts on a metal-filled material (corresponding to claim 12).

The method for establishing osteoblasts on a metal material embedded in a bone in the body according to claim 12, wherein the discharge rate of hydrogen peroxide solution discharged from the injection device is 100 CC / min or less (corresponding to claim 13). ).

The method for establishing osteoblasts on a bone-implanted metal material in the body according to claim 12 or 13, wherein the amount of ultraviolet rays or near-ultraviolet rays emitted from an irradiation device such as ultraviolet rays is 0.1 milliwatt or more. Corresponding to claim 14).

In addition to the above characteristics, claims 12 to 14 have a concentration of hydrogen peroxide of 1 w / v% or more and 7 w / v% or less, and a concentration of hydrogen peroxide stabilizer of 81 ppm (mg / L) or less in this aqueous solution. The method for colonizing osteoblasts on a metal material embedded in a bone in the body according to any one of the above (corresponding to claim 15).

The fifteenth aspect of claim 15, in addition to the above-mentioned characteristics, the concentration of the hydrogen peroxide is 1 w / v% or more and 7 w / v% or less, and the concentration of the hydrogen peroxide stabilizer is 0 ppm (mg / L) in this aqueous solution. A method for establishing osteoblasts on a metal material embedded in a bone (corresponding to claim 16).

The method for establishing osteoblasts on a metal material embedded in a bone in the body according to claim 15 or 16, wherein the concentration of hydrogen peroxide is 2 w / v% or more and 6 w / v% or less in addition to the above-mentioned characteristics (corresponding to claim 17). ).

The method for establishing osteoblasts on a metal material embedded in a bone according to claim 15 or 17, wherein the hydrogen peroxide stabilizer is one or more of phenacetin and acetanilide in addition to the above-mentioned characteristics (claim 18). Correspondence).

The osteoblast colonization on a bone-implanted metal material in the body according to any one of claims 15 to 18, in which the impurity heavy metal content is only 0.001 w / v% or less with respect to hydrogen peroxide in addition to the above-mentioned characteristics. Processing method (corresponding to claim 19).

According to the configuration of the present invention, hydrogen peroxide, which is harmless even in the human body after implanting, is supplied to the implant implanting portion, and UV irradiation is performed here by scattering and condensing, and the surface of the metal material embedded in the bone inside the body. In the art, it is possible to provide an osteoblast colonization treatment apparatus on a bone-implanted metal material in the body, which efficiently treats the surface of an implant member by generating a hydroxyl radical and improves osteoblast colonization and proliferation.

Conceptual diagram of the stand-alone in-vivo bone-embedded metal material osteoblast colonization treatment apparatus of the first embodiment Functional block diagram of the injection device in the stand-alone body-embedded metal material osteoblast colonization processing device of the first embodiment. The figure which shows the structural example of the stand-alone injection apparatus of Embodiment 1. FIG. 3 is a diagram showing a configuration example of the tip of the injection device of FIG. 3 (A). External view of the irradiation device such as ultraviolet rays in the stand-alone body bone-embedded metal material top osteoblast colonization treatment device of the first embodiment. Functional block diagram of an ultraviolet irradiation device in the stand-alone body-embedded metal material osteoblast colonization treatment device of the first embodiment The figure which shows the structural example which scatters to the irradiation port of the irradiation apparatus such as ultraviolet rays in the osteoblast fixation processing apparatus on the stand-alone body bone implant metal material of Embodiment 1. The figure which shows the structural example which condenses light on the irradiation port of the irradiation apparatus such as ultraviolet rays in the stand-alone body bone implanting metal material top osteoblast colonization processing apparatus of Embodiment 1. Conceptual diagram of the integrated osteoblast colonization processing apparatus on the bone-embedded metal material in the body of the first embodiment The figure for demonstrating the irradiation discharge port in the osteoblast colonization processing apparatus on the integrated body bone implant metal material of Embodiment 1. Flow chart of the process of the osteoblast colonization processing apparatus on the bone-embedded metal material in the body of the first embodiment The figure which shows the influence which the radical treatment of Embodiment 1 has on a titanium surface. The figure which shows the proliferation of osteoblasts on the surface of titanium subjected to radical treatment of Embodiment 1. The figure which shows the proliferation of osteoblasts on the surface of titanium subjected to radical treatment of Embodiment 1. The figure which shows the influence which the radical treatment of Embodiment 1 has on the surface of titanium contaminated with bacteria. The figure which shows the proliferation of osteoblasts on the surface of the bacterially contaminated titanium which was radically treated with Embodiment 1. FIG. The figure which shows the proliferation of osteoblasts on the surface of titanium subjected to radical treatment of Embodiment 1. The figure which shows the state of extension of the cell morphology of the cell experiment of Embodiment 1. Hydroxyl radical radical generation analysis result of Embodiment 1 The figure which shows the configuration example of the treatment apparatus Conceptual diagram of radical generation from the hydrogen peroxide solution of the second embodiment Analysis result of high performance liquid chromatography (HPLC) before laser irradiation of hydrogen peroxide aqueous solution A having a phenacetin concentration of 81 ppm according to the second embodiment. Analysis result of high performance liquid chromatography (HPLC) after laser irradiation of hydrogen peroxide aqueous solution A having a phenacetin concentration of 81 ppm according to the second embodiment. Analysis result of high performance liquid chromatography (HPLC) before laser irradiation of hydrogen peroxide aqueous solution F having a phenacetin concentration of 344 ppm according to the second embodiment. Analysis result of high performance liquid chromatography (HPLC) after laser irradiation of hydrogen peroxide aqueous solution F having a phenacetin concentration of 344 ppm according to the second embodiment. Analysis result of high performance liquid chromatography (HPLC) before laser irradiation of hydrogen peroxide aqueous solution J having an acetanilide concentration of 177 ppm according to the second embodiment. Analysis result of high performance liquid chromatography (HPLC) after laser irradiation of hydrogen peroxide aqueous solution J having an acetanilide concentration of 177 ppm according to the second embodiment. The figure for demonstrating the treatment of the implant surface of Embodiment 1.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. The content of the present invention is not limited to the following embodiments, and may be implemented in various embodiments within the scope of the gist of the present invention.

In the following, an example in which an implant is used for the metal material for bone implantation in the body will be described as an osteoblast colonization treatment device for the metal material for bone implantation in the body.
<Embodiment 1>

In the present embodiment, there are an independent type in which the hydrogen peroxide solution discharge port and the ultraviolet ray irradiation port are independent and independent, and an integrated type in which the hydrogen peroxide solution discharge port and the ultraviolet ray irradiation port are integrated. In the following, the stand-alone type and the integrated type will be described separately.
<Embodiment 1 Stand-alone outline>

Basically, it is a device that improves the fixation and proliferation of osteoblasts on the metal material embedded in the body, and is a device that is independent of the hydrogen peroxide solution discharge port and the ultraviolet irradiation port.
<Embodiment 1 Stand-alone specific configuration>

The stand-alone configuration is an osteoblast colonization treatment device on a metal material embedded in a bone in the body, which has a hydrogen peroxide solution discharge port and an ultraviolet light irradiation port as constituent requirements. The configuration requirements and related elements will be described below.
<Embodiment 1 Stand-alone discharge port>

The "hydrogen peroxide solution discharge port" includes an opening for discharging hydrogen peroxide solution and a tip portion of a nozzle constituting the opening. The opening shape of the hydrogen peroxide solution discharge port is basically circular, but is not necessarily limited to this, and may be elliptical or rectangular. Further, the peripheral edge of the opening may be configured simply like the edge of a cylinder, but may have a nozzle shape that entrains air with a negative pressure so as to entrain air from the outside according to the flow velocity of the hydrogen peroxide solution. .. Further, although it is basically composed of metal, it may be composed of a substance that does not easily react with hydrogen peroxide solution such as ceramics, or an elastic material such as silicon rubber. If it is made of an elastic material such as silicone rubber, it will be easier to push into the place where the side surface of the implant is intricate with the gingiva or the jawbone. Further, although the tip portion is made of silicon rubber, a metal ring that reacts to X-rays may be fitted to the tip so that the treatment can be performed while taking an X-ray. Further, it is preferable that the tip portion of the nozzle is made of a substance that does not easily react with the hydrogen peroxide solution. Ceramic materials and metals with a coated surface. Of course, it can also be made of a metal having low reactivity, such as stainless steel.

As shown in FIG. 1, an implant (dental implant) 0100 is placed in the jawbone 0101, and hydrogen peroxide solution is put into the gap between the implant 0100 and the gingiva 0104 from the nozzle 0102 (in the direction of the arrow in FIG. 1). The hydrogen oxide is irradiated with ultraviolet rays such as laser light from the chip 0103 (in the direction of the arrow in FIG. 1). Hydrogen peroxide is a liquid, and as a supply form, a method of spraying in the form of a mist or a method of dropping the liquid can be considered. The place where you want to settle osteoblasts is the surface of the implant that is contaminated with bacteria or not contaminated with bacteria, especially hydrogen hydrogen and ultraviolet rays, etc., mainly near the bottom of the pocket (the groove between the implant and the gingiva). Although it is discharged and irradiated, it is desirable to discharge and irradiate the entire exposed implant surface with hydrogen, hydrogen, and the like. Ultraviolet rays and the like are basically irradiated with the irradiation discharge port facing the implant surface. Preventive Dentistry may promote the colonization of osteoblasts by ejecting and irradiating the surface of an implant that is not contaminated with bacteria with hydrogen peroxide, ultraviolet rays, or the like. Here, as the implant material, in addition to metals such as titanium, cobalt-chromium alloy, and titanium alloy, alumina, ceramic, zirconia, apatite, and the like are used. Further, in the example of FIG. 1, the implant surface is irradiated with ultraviolet rays or the like while the pocket is filled with hydrogen peroxide or the implant surface is wet with hydrogen peroxide.
This makes it possible to improve the colonization and proliferation of osteoblasts with respect to the metal material (implant) embedded in the body.
<Embodiment 1 Stand-alone discharge port-related element>

The above is a description of the discharge port, but elements related to this will be described below.
<Embodiment 1 Stand-alone discharge port-related element Nozzle portion leading to the nozzle tip portion>

The basic material may be the same as that of the tip of the nozzle. The difference between the nozzle tip and the nozzle leading to it is the inner diameter. The nozzle tip portion has an inner diameter of about 200 microns, but the portion up to that portion may have a sufficient inner diameter. That is, as shown in FIG. 3B, the tip of the nozzle has a double taper shape, and the hydrogen peroxide solution supply side of the tip 0305 has an outer diameter of about 0.35 mm (350 μm), and the diameter gradually increases. The discharge port 0306 has a structure with an outer diameter of about 0.2 mm (200 μm). The ultra-small discharge port 0306 has a structure that makes it easy to inject hydrogen peroxide solution into the gap between the implant 0100 and the jawbone 0101 (the gap between the gingiva 104) shown in FIG. By narrowing the inner diameter toward the tip, the discharge pressure of hydrogen peroxide solution from the nozzle tip opening can be increased. Further, the portion leading to the nozzle tip portion may have a curve in the middle. The curved shape makes it easier to insert the tip into the delicate gap between the gingiva and the implant.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery part tank>

Fill the tank with hydrogen peroxide solution. This may be a cartridge type or a type in which hydrogen peroxide solution is transferred from a bottle or the like. However, the cartridge type is preferable from the viewpoint of safety and cleanliness. Further, for the chemical stability of the hydrogen peroxide solution, it is preferable to give the tank a light-shielding property. Further, it is preferable that a temperature control device is provided so as to keep the temperature constant. Further, it is preferable that the remaining amount of the hydrogen peroxide solution in the tank can be detected by measuring its weight or the liquid level by an optical sensor. In addition, the tank can be configured to be equipped with multiple cartridges so that additional hydrogen peroxide solution can be replenished, or to prevent sudden depletion of hydrogen peroxide solution during medical treatment, and the delivery cartridge can be switched automatically. It is preferable to configure it so that it can be used.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery part Solenoid valve>

The solenoid valve is controlled in principle by a control unit described later. The solenoid valve is the part that serves as a barrier for the hydrogen peroxide solution from the tank to flow to the nozzle, and even if the pump is driven by closing this solenoid valve, the hydrogen peroxide solution is instantaneously discharged. It is possible to stop. This control is opened and closed via the control unit by a remote controller operated by the practitioner. The opening and closing of the solenoid valve may be configured to have an intermediate state in addition to the completely open state and the completely closed state. Further, it is preferable that this solenoid valve is also made of a material that does not react with hydrogen peroxide solution. The materials are as described above. Further, the solenoid valve may be formed over a plurality of stages, and if it can be said that the hydrogen peroxide flow paths are provided in parallel, it is necessary to provide each flow path. It is preferable that a manual valve is provided in addition to the solenoid valve. Further, it is preferable that the solenoid valve is designed to be closed in the event of a power failure. This is to prevent the hydrogen peroxide solution from being left out.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery part pump>

The pump must be constructed of a material that does not contaminate the hydrogen peroxide solution. It is also necessary to configure the hydrogen peroxide solution so that it does not decompose. For this purpose, the rotation speed of the rotary blades of the pump and the material of the rotary blades are selected. The lower the rotation speed of the rotary blades of the pump, the more the decomposition of the hydrogen peroxide solution can be prevented. Is preferable. Further, when adjusting the flow rate, the rotation speed may be controlled for each of a plurality of stages. The flow velocity and flow rate can be finely adjusted by stopping the final stage or stopping the first stage. Further, from the viewpoint that the material of the blade is less likely to cause a chemical reaction, it is preferable to use a material having low chemical reactivity such as Teflon (registered trademark) as the surface material. It is also conceivable to use a bellows type pump instead of using blades. This is because, in this type, the blades locally generate a high pressure in the liquid hydrogen peroxide solution, whereas the entire liquid can be run at the same pressure.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery part Power supply>

The power supply is preferably an uninterruptible power supply in case of a sudden power failure. For example, although power is supplied from the outside, it is conceivable to provide a storage battery to prevent a momentary decrease. Further, the power output may be made variable according to the drive of the pump. This is to reduce power consumption and prevent the pump from being overloaded.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery part Control unit>

The control unit is provided with a function to control a pump, a solenoid valve, or a sensor, a communication function, etc. related to these. Basically, regarding the discharge of hydrogen peroxide solution and the stop of discharge, a control signal is output to a pump, a solenoid valve, etc. according to a signal from a remote controller operated by the practitioner. Further, it is preferable to provide an emergency stop mode so as to stop the outflow of hydrogen peroxide solution in the event of some trouble. For example, a hydrogen peroxide solution detection sensor that detects that it is hydrogen peroxide solution is provided in the flow path so that the outflow is stopped when it is determined that the flowing liquid is not hydrogen peroxide solution. Can be designed to control pumps, hydrogen peroxide. Furthermore, the temperature of the hydrogen peroxide solution is measured by a temperature sensor, and even if the temperature of the circulating hydrogen peroxide solution deviates from a predetermined range, the pump for circulating the hydrogen peroxide solution is stopped or the electromagnetic valve is turned on. It is conceivable to control it to close. Further, when the temperature reaches a predetermined temperature, the pump may be operated again to control the solenoid valve in the open state.
<Embodiment 1 Stand-alone discharge port-related element Hydrogen peroxide solution delivery portion Others>

Since the flow path of the hydrogen peroxide solution needs to be kept clean at all times, an automatic cleaning function may be provided. This is because the flow path is contaminated by germs in the air when the device is not used for a certain period of time. For example, an alcohol tank may be provided so that alcohol can be circulated throughout the flow path of the device. Further, in order to minimize the growth of germs in the flow path, a blocking portion may be provided to block the flow path from the outside air. It is conceivable that this cutoff portion is provided at the rear end portion of the nozzle, and the nozzle is designed to be replaceable. The nozzle portion may be replaceable or replaceable and disposable because it is exposed to the human body. The basic part for issuing commands to the control unit is the remote controller used by the practitioner, but it is preferable to provide the operation buttons of the remote controller as close to the hydrogen peroxide solution distribution path as possible. This is because in the present embodiment, both hands of the practitioner are blocked because the hydrogen peroxide solution discharge flow path and the ultraviolet irradiation path are separate bodies. Therefore, it is preferable that the operation buttons related to the hydrogen peroxide solution are provided on the hydrogen peroxide solution distribution path because they can be intuitively operated.

As shown in FIGS. 2 and 3A, the injection device 0200 includes a hydrogen peroxide solution tank 0201 for storing hydrogen hydrogen solution, an injection port 0202 for injecting hydrogen hydrogen solution, and hydrogen peroxide. A valve 0203 as an electromagnetic valve for injecting the hydrogen peroxide solution of the water tank 0201, a pump 0204 for sending out the hydrogen peroxide solution to the outside, and a hydrogen peroxide solution flow tube 0205 for circulating the hydrogen peroxide solution. Discharge port 0206 for discharging hydrogen oxide water to the affected area (for example, affected area such as peri-implantitis), controller 0207 for controlling valve 0203 and pump 0204, and power supply 0208 for supplying power to valve 0203, pump 0204, and controller 0207. It is composed of and.

Under the control of the controller 0207 of the injection device 0200, hydrogen peroxide solution is discharged from the discharge port 0206 to the patient's implant in a fixed amount, for example, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes and a predetermined time. Will be done. Here, the discharge rate of the hydrogen peroxide solution discharged from the injection device is 100 CC / min or less.
At the same time as the discharge of hydroxyl radical from the discharge port 0206 of the injection device 0200, one or more of ultraviolet rays, near-ultraviolet rays, and blue visible light are emitted from the irradiation port provided at the tip of the pen-shaped main body of the irradiation device such as ultraviolet rays. It was found that when irradiated with UV light, hydroxyl radicals are efficiently generated, so that the fixation and proliferation of osteoblasts around the implant are improved.
ing.
<Embodiment 1 Stand-alone irradiation port>

The "irradiation port" includes an opening and a tip portion of a chip constituting the opening. The irradiation port irradiates ultraviolet rays or the like. Irradiation is basically performed through a transparent member. Since the transparent member needs to be a member that transmits ultraviolet rays and the like, it is made of quartz, a silicone-based material, or the like. The amount of ultraviolet light is preferably 0.1 milliwatt or more. Further, the transparent material portion of this opening portion may be replaceable. It is also replaceable and may be disposable. This part is in contact with the human body and is for the prevention of infectious diseases. Further, the transparent material portion may be provided with a metal marker for observing with X-rays in a part thereof.
<Embodiment 1 Stand-alone irradiation port-related element>

The elements related to the irradiation port will be described below.
<Embodiment 1 Stand-alone irradiation port-related element Chip portion leading to the tip tip portion>

In principle, the chip portion leading to the chip tip portion contains an optical fiber for transmitting ultraviolet rays and the like. This optical fiber is connected from a light source such as ultraviolet rays. It is preferable that the connection portion of the tip portion of the chip with the replaceable or disposable transmissive material portion is filled with a gel-like substance that is transparent and transmits ultraviolet rays and the like. This is to reduce the conduction loss of ultraviolet rays and the like. Further, since the optical axes need to be aligned with each other, it is preferable that the transmission material portion at the tip of the chip and the optical fiber have a configuration in which the axes can be easily aligned. It is preferable to have a structure like a so-called ferrule.
<Embodiment 1 Stand-alone irradiation port-related element Laser light source such as ultraviolet rays>

The laser light source such as ultraviolet rays is preferably an ultraviolet LED light source, but since ultraviolet rays are difficult to grasp with the naked eye, near ultraviolet rays or blue visible light may be used. Of course, it may be a mixture of ultraviolet rays and visible light. Further, it is conceivable to emit visible light to confirm the irradiation position of the implant, and to use only ultraviolet light without emitting visible light at the time of treatment. Targeting is performed with visible light, the position is confirmed, and the treatment is performed with ultraviolet light. In addition, visible light is blinked to make it easier to grasp where the light is shining, and visible light and ultraviolet light are alternately irradiated in a short period of time so that the targeting position can always be grasped. May be good.
<Embodiment 1 Stand-alone irradiation port-related element Laser light guide path such as ultraviolet rays>

Laser light guide paths such as ultraviolet rays are composed of optical fibers. In principle, use a material that can reduce the loss of light with a short wavelength among the most used light. Further, when two or more types of light sources are used, the light guide path can be designed so as to integrate two or more paths near the tip of the chip having the irradiation port. Further, it is also possible to provide a lens near the tip of the chip and conversely provide a path for acquiring an image near the tip of the chip. This is because information on the surface condition of the implant can be obtained from the image near the tip of the tip. This image does not necessarily have to be an image, and may be blurred. This is because even if it is blurred, it is possible to grasp the implant and the surrounding condition of the implant by statistical processing. Furthermore, it is also possible to use artificial intelligence technology to grasp this situation.
<Embodiment 1 Stand-alone irradiation port-related element Power supply such as ultraviolet rays>

The power source such as ultraviolet rays basically needs to be a stabilized power source. Further, the output may be controlled in order to change the amount and intensity of ultraviolet rays and the like. This control is performed based on a signal from a control unit described later.
<Implementation 1 Stand-alone irradiation port related element control unit>

The control unit basically receives the operation signal of the practitioner from a remote controller or the like to control the ultraviolet emission system. The main control targets are light sources such as ultraviolet rays and power supplies. However, as described above, in the case where blinking is repeated at predetermined intervals and in the case where ultraviolet rays and visible rays are alternately emitted, it is configured to be controlled based on programming. In this case, a signal from a crystal oscillator having a timekeeping function is used.

FIG. 4 shows a schematic configuration of an ultraviolet irradiation device, and FIG. 5 shows a detailed configuration of the ultraviolet irradiation device of FIG. Hereinafter, the configuration operation of the ultraviolet irradiation device will be described with reference to FIGS. 4 and 5.

As shown in FIG. 4, the ultraviolet irradiation device 0400 is provided with one or more of ultraviolet rays, near-ultraviolet rays, and blue visible light (hereinafter referred to as “ultraviolet rays, etc.”) on the end face of the tip nozzle 0401 of the pen-shaped main body. Irradiation is possible from the irradiation port (irradiation surface) 0402.

The ultraviolet irradiation device 0402 is set in the charger 0403 and connected to an external power source (not shown) via the power cable 0404 to charge the ultraviolet irradiation device 0400. In the example of FIG. 4, the ultraviolet irradiation device 0402 is divided into an operation unit having a built-in light source for irradiating ultraviolet rays and the like to operate the device, and a battery unit having a built-in rechargeable battery. The operation unit and the battery unit have a separable structure, and when the device is out of charge, it can be replaced with a spare battery. This allows the dentist to continue the procedure on the patient. Here, the ultraviolet irradiation device 0400 is a cordless type device, but it may be a type that does not have a rechargeable battery and directly supplies power via a power cable drawn from the device. Further, it may be possible to use both a battery and a power supply.
Can be replaced with a battery. This allows the dentist to continue the procedure on the patient. Here, the ultraviolet irradiation device 0400 is a cordless type device, but it may be a type that does not have a rechargeable battery and directly supplies power via a power cable drawn from the device. Further, it may be possible to use both a battery and a power supply.

As shown in FIG. 5, the ultraviolet irradiation device 0500 includes an ultraviolet light source 0501 such as an LED that emits ultraviolet rays, a condenser lens 0502 that collects ultraviolet rays, an optical fiber 0503 that guides ultraviolet rays, and an optical fiber 0503. It is composed of a lens 0504 as an irradiation port (irradiation surface) for irradiating ultraviolet rays and the like guided by the above, a controller 0505 that controls irradiation of ultraviolet rays and the like, and a power supply 0506 connected to the controller 0505.

The ultraviolet rays and the like emitted from such an ultraviolet irradiation device 0500 are any one or more of ultraviolet rays, near-ultraviolet rays, and blue visible rays. As the wavelength of the light beam, wavelengths of 365 nm, 400 nm, and 465 nm can be used. In the example of FIG. 5, an example using a plurality of LEDs is shown, but one or more LEDs may be used, and two or three LEDs can be selectively adopted. Therefore, a two-wavelength type of a blue LED (about 465 nm) and a purple LED (about 400 nm) or a one-wavelength type of an LED (365 nm) may be used. Here, the amount of ultraviolet rays or near-ultraviolet rays irradiated from the irradiation device such as ultraviolet rays is 0.1 milliwatt or more in consideration of the influence on the human body.
<Embodiment 1 Stand-alone irradiation port-related element Tip lens 1>

The lens at the tip can be configured to scatter and irradiate light from a light source.

As shown in FIG. 6, the osteoblast fixation treatment apparatus on the metal material embedded in the body of the present embodiment is a light beam (laser light) such as ultraviolet rays from an ultraviolet ray irradiation port (irradiation surface) 0601 of the ultraviolet light irradiation device. The 0602 may be configured to be scattered through a scattering surface 0603 such as a frosted glass, and the scattered light 0604 may be light scattered to the implant 0605. In the case of light traveling straight, it is difficult for the light to wrap around to the thread of the implant or the part shaded by the gingiva, but it is easier to wrap around by using scattered light.
<Embodiment 1 Stand-alone irradiation port-related element Tip lens 2>

The lens at the tip can be configured to focus and irradiate the light from the light source.

Further, as shown in FIG. 7, the osteoblast fixation treatment device on the bone-embedded metal material in the body of the present embodiment emits light rays such as ultraviolet rays from the ultraviolet ray irradiation port (irradiation surface) 0701 of the ultraviolet ray irradiation device. , The condensing lens 0703 may be used to condense the light, and the condensing light 0704 may be condensed on the implant 0705. When it is possible to irradiate ultraviolet light etc. with the implant relatively exposed, it is more efficient to collect the light at the target place as much as possible. It is effective to irradiate.
<Embodiment 1 Integrated Overview>

Basically, it is a device that improves the fixation and proliferation of osteoblasts in a metal material embedded in the body, and is a device in which a hydrogen peroxide solution discharge port and an ultraviolet irradiation port are integrated.
<Embodiment 1 Integrated Specific Configuration>

The integrated configuration is an osteoblast colonization treatment device on an implantable metal material, which has an irradiation discharge port in which a hydrogen peroxide solution discharge port and an irradiation port such as ultraviolet rays are integrated as a constituent requirement. The configuration requirements and related elements will be described below.
<Embodiment 1 Integrated Irradiation Discharge Port>

The "irradiation discharge port" includes an opening for irradiating ultraviolet rays and the like, an opening for discharging hydrogen peroxide solution, and a tip portion of a chip constituting these openings. The opening shape of the irradiation discharge port is basically a circular structure having a double structure having an opening of the discharge port around the opening of the irradiation port, but is not necessarily limited to this, and may be an elliptical shape or a rectangular shape. There may be. Further, the peripheral edge of the opening may be configured simply like the edge of a cylinder, but may have a chip shape that entrains air with a negative pressure so as to entrain air from the outside according to the flow velocity of the hydrogen peroxide solution. .. Since the irradiation port portion is the same as the material of the irradiation port described in the stand-alone type, the description thereof will be omitted. Further, since the discharge port portion is the same as the material of the discharge port described in the stand-alone type, the description thereof will be omitted.

As shown in FIGS. 8A and 8B, an implant (dental implant) 0800 is implanted in the jawbone 0801, and the gap between the implant 0800 and the gingiva 0804 is irradiated with ultraviolet rays or the like from the integrated tip 0802 and peroxidation. Hydrogen water is discharged (released). FIG. 8A shows the case of non-surgical procedure, and FIG. 8B shows the case of surgical procedure. Regardless of non-surgical procedure or surgical procedure, the surface of the implant is washed with hydrogen peroxide and at the same time irradiated with ultraviolet rays. In the case of surgical treatment, since a wide surgical field can be secured, there is an advantage that the irradiation treatment of the implant surface can be efficiently performed by using a device having a large irradiation discharge port. As shown in FIG. 27, treatment is performed when peri-implantitis occurs from the initial stage (healthy state) of implant placement, a pocket is formed between the implant and the gingiva, and the bone around the implant is lost. Here, the non-surgical procedure is a method of inserting an instrument into the pocket of peri-implantitis for treatment, and the surgical procedure is a method of incising the gingiva with a scalpel or the like (not shown) and performing the treatment with the gingiva peeled off. be. Regardless of non-surgical procedure or surgical procedure, the implant surface is treated by irradiation with hydrogen peroxide and ultraviolet rays.
This makes it possible to improve the colonization and proliferation of osteoblasts with respect to the metal material (implant) embedded in the body. Here, as the implant material, in addition to metals such as titanium, cobalt-chromium alloy, and titanium alloy, alumina, ceramic, zirconia, apatite, and the like are used.
<Embodiment 1 Integrated Irradiation Discharge Port Related Elements>

The above is a description of the irradiation discharge port, but elements related to this will be described below.
<Embodiment 1 Integrated Irradiation Discharge Port Related Element Chip portion leading to the tip tip portion>

The chip part discharges hydrogen peroxide solution from the irradiation discharge port, and irradiates the discharged hydrogen peroxide solution with ultraviolet rays (laser light) to efficiently generate hydroxy radicals. A flow path for hydrogen peroxide solution is provided as a separate route.

As shown in the lower figure of FIG. 9, the tip portion 0902 at the tip has a hollow tube structure 0905, an optical fiber 0904 is built in, support members are installed at several places (not shown), and a hollow portion around the optical fiber 0904. It is equipped with a flow path 0906 that guides and flows hydrogen peroxide solution from the optical fiber and a light guide (not shown) that guides laser light (ultraviolet rays, etc.) emitted from a light source (not shown) into the optical fiber 0904. The mechanism is such that laser light (ultraviolet rays, etc.) and hydrogen peroxide solution can be emitted simultaneously from the outlet 0901. FIG. 9 The example in the lower figure shows an example in which irradiation with ultraviolet rays or the like is performed by scattered light (see FIG. 6). Hydrogen peroxide is a liquid, and as a supply form, a method of spraying in the form of a mist or a method of dropping the liquid can be considered. The supply form of hydrogen peroxide is not limited, but it is important to irradiate the implant surface with ultraviolet rays or the like while the surface of the implant is wet with hydrogen peroxide.
<Embodiment 1 Integrated Irradiation Discharge Port Related Elements Part Up to Chip>

As shown in the upper figure of FIG. 9, a guide tube 0903 (inducing ultraviolet rays and hydrogen peroxide solution by another route) connected to an irradiation device such as ultraviolet rays and an injection device (not shown) and a tip coupled to the guide tube 0903. A tip portion 0902 and an integrated tip irradiation discharge port 0901 are provided at the end of the tip portion 0902.
<Embodiment 1 Integrated Control Unit>

The control unit basically receives the operation signal of the practitioner from a remote controller or the like to control the ultraviolet emission system. The main control targets are light sources such as ultraviolet rays and power supplies. Since the control of the laser light source such as ultraviolet rays and the control of the power source such as ultraviolet rays are the same as those described in the stand-alone type, the description thereof will be omitted.

Hereinafter, the method for establishing osteoblasts on a metal material embedded in a bone in the body according to the first embodiment will be described with reference to FIG.
First, the hydrogen peroxide solution ejection step of ejecting the hydrogen peroxide solution into the gap between the patient's implant and the jawbone in which the implant is embedded (the gap with the gingiva) is executed (step 1001).
While discharging the hydrogen peroxide solution, an irradiation step of ultraviolet rays or the like that irradiates one or more scattered light of ultraviolet rays, near ultraviolet rays, and blue visible rays (ultraviolet rays or the like) from the irradiation port of ultraviolet rays or the like is executed (step 1002). ).

The procedure for executing the hydrogen peroxide solution discharge step 1001 and the ultraviolet irradiation step 1002 may be performed in reverse or at the same time.

This can improve the colonization and proliferation of osteoblasts around the patient's implant.
<Embodiment 1 Other Specific System Configuration>

As shown in FIG. 19, in a dental clinic, a patient 1902 lies on a dental treatment device 1903, and a dentist 1901 performs a dental treatment. The treatment device 1903 is connected to a receipt computer system (not shown) via a network (including a wired LAN, a wireless LAN, the Internet, a broadband, and a mobile network). This receipt computer system can be implemented by software on a computer in a dental office, a remote computer, or by dedicated hardware. The treatment device 1903 includes a liquid crystal touch panel display 1904, a display 1905 that displays dental roentgens, CT scan images, etc., an LED shadowless lamp 1906 that brightly illuminates the oral cavity, a treatment device control unit 1907, and a support arm 1908 that supports the display 1905. It is equipped with a support arm 1909 for the LED shadowless lamp 1906, a cutting drill 1910, an intraoral vacuum 1911, a treatment table table 1912, and the like. The display 1905 and the LED shadowless lamp 1906 have a structure that can be adjusted to a position where the dentist 1901 can easily perform the operation by the support arm 1908 and the support arm 1909, respectively.

The injection device and the irradiation device such as ultraviolet rays have an IoT function and are connected to the receipt computer system by wire or wirelessly, and the treatment information is automatically transmitted to the receipt computer and used for automatic collection of receipts, or at own expense. It can be used for medical treatment and insurance claims.
<Embodiment 1 Effect on osteoblast colonization and proliferation>
<Experimental method and experimental results>

Hereinafter, the experimental method and the experimental result in the osteoblast colonization processing apparatus on the bone-implanted metal material in the body will be described. In the following experiments, titanium was used as a sample. Since the following abbreviations are used in FIGS. 11 to 16 described later, the description will be supplemented. H (-) L (-): Indicates a group in which a sample is immersed in pure water and treated in a light-shielded state (a group in which hydrogen peroxide is not used and UV LED irradiation is not performed). H (+) L (-): The sample is immersed in 3% hydrogen peroxide and treated in a light-shielded state (treatment with only hydrogen peroxide solution), and H (-) L (+): The sample is immersed in pure water and LED irradiation is performed (LED). (Treatment by irradiation only) is shown, and H (+) L (+): a sample is immersed in 3% hydrogen peroxide and LED irradiation is performed (hydrogen peroxide photodecomposition method or radical treatment).
<Titanium sample>

The surface of a pure titanium disk-shaped sample (Grade 4, TB550, Nishimura Metal) with a diameter of 5 mm and a thickness of 2 mm was treated by sandblasting and acid etching to give a rough surface similar to the surface of a dental implant for experiments. Using. Sandblasting was performed by spraying 250 μm alumina particles at 0.4 MPa. Then, it was immersed in 49% sulfuric acid at 60 ° C. for 1 hour for acid etching. After the treatment, the sample was immersed in ultrapure water for 10 minutes, immersed in acetone for 10 minutes, and finally immersed in ultrapure water again for 10 minutes for ultrasonic cleaning. As a result of measuring the surface roughness of the prepared titanium sample using an optical interferometer (Talysurf CCI HD, Taylor Hobson), Sa (arithmetic mean roughness) was 1.97 μm, Sq (root mean square height) was 2.48 μm, It was confirmed that the Sdr (ratio of the developed area of the interface) was 40.07% and the Sds (number density of apex) was 0.071 / μm2, which were similar to the surface roughness of the dental implant. The prepared samples were autoclaved at 121 ° C for 15 minutes and divided into the following two groups: 1) a new titanium sample (New-Ti) and 2) a 4-week aged titanium sample (Aged-Ti). New-Ti was used in the experiment the day after acid etching, cleaning and autoclaving. On the other hand, Aged-Ti was aseptically stored in an incubator at 37 ° C for 4 weeks before use in the experiment, and after aging treatment, it was used in the experiment.
<Surface treatment of titanium sample by hydrogen peroxide photodecomposition method>

The surface of the titanium sample was treated with LED irradiation and 3% hydrogen peroxide alone or in combination for 5 minutes. Each group was divided into the following four groups according to the treatment method: 1) H (-) L (-), H (+) L (-), H (-) L (+), and H (+) L. (+). For H (+) treatment, the sample was immersed in 300 μL of 3% hydrogen peroxide in the wells of a 48-well cell culture plate. On the other hand, in the H (-) treatment, the sample was immersed in 300 μL of pure water. In the L (+) treatment, the sample was irradiated with 365 nm LED light, and in the L (-) treatment, the 48-well cell culture plate containing the sample was placed in a light-shielding box. The device used as a light source was an LED spot-curing device (OmniCure LX400; Lumen Dynamics Group), which was irradiated with light at an irradiance of 1000 mW / cm2. After the treatment, the sample was washed twice with pure water and then used in each experiment.
<Experiment 1>
<Analysis of surface chemicals>

The effect of radical treatment on the titanium surface will be described with reference to FIG. FIG. 11 shows the analysis results of surface chemical substances.

The chemical composition of the sample surface was analyzed by X-ray photoelectron spectroscopy (XPS; JPS-9010MC, JEOL). For analysis, untreated New-Ti, H (+) L (+) treated New-Ti and H (-) L (-), H (+) L (-), H (-) L ( Aged-Ti treated with +) or H (+) L (+) was used. XPS measurements were performed under 10 kV and 10 mA conditions and irradiated with Mg-Kα X-rays with a spot size of 1 mm. The obtained spectrum was analyzed by the software (SpecXPS, JEOL) attached to the device. Measurements were performed using 4 samples in each group.
<Evaluation of wettability of sample surface>

New-Ti and Aged-Ti untreated or treated with H (+) L (+) were used for the analysis. The contact angle when 0.4 μL of pure water was dropped on the sample surface was measured using a contact angle meter (CA-X, Kyowa Surface Science). Measurements were performed using 6 samples in each group.

FIG. 11A shows the XPS analysis result of the titanium surface. Here, the vertical axis indicates intensity, and the unit is cps (count per second). cps means the intensity of photoelectrons captured by the detector per second. The horizontal axis shows the binding energy (eV). The XPS spectra of the newly produced titanium subjected to radical treatment "H (+) L (+)" and the titanium aged at 37 ° C for 4 weeks are shown. FIG. 11B shows the result of quantitative analysis of carbon content based on the XPS spectrum. Here, the vertical axis shows the atomic percentage (%), and the horizontal axis shows the comparative experiment between the newly manufactured titanium and the aged titanium. It was found that the carbon content on the surface of titanium increases due to aging, but the carbon content decreases to the same level as the newly manufactured titanium due to radical treatment. FIG. 11C shows the result of the contact angle measurement of the titanium surface. Here, the vertical axis shows the contact angle (degrees), and the horizontal axis shows a comparative experiment between the newly manufactured titanium and the aged titanium. It was found that the new titanium surface has a small contact angle and is hydrophilic, while the aged titanium surface is hydrophobic. However, it was found that the hydrophilicity was restored by radical treatment.
<Statistical analysis>

Statistical analysis of quantitative analysis results was performed using JMP Pro 11.0 (SAS Institute). Two-group comparison was performed by Student-t test, and multiple comparison was performed by Tukey-Kramer honesty significant difference test after one-way ANOVA. The significance level of the test was 5% in all analyses. In FIGS. 11B and 11C, the different alphabets indicate statistically significant differences between the groups.
<Experiment 2>
<Cell proliferation test>

The proliferation of osteoblasts on the radically treated titanium surface will be described with reference to FIGS. 12 and 13. 12 and 13 show the cell proliferation test results.

Experiments were conducted using mouse-derived osteoblast-like cells (MC3T3-E1) provided by the Cell Materials Development Office of RIKEN. Cells were cultured in alpha-modified Eagle's medium (α-MEM; Nacalai Tesque) containing 10% fetal bovine serum, 100 U / mL penicillin, and 0.1 mg / mL streptomycin. When the state of 80% confluence was reached, the cells were detached with 0.25% trypsin-EDTA (Thermo Fisher Scientific) and used in the experiment. As a bone formation medium, 50 μg / mL ascorbic acid (Wako Pure Chemical Industries, Ltd.), 10 mM β-glycerophosphate sodium (Sigma Aldrich), and 0.01 μM dexamethasone (Wako Pure Chemical Industries, Ltd.) were added to the above α-MEM. Then, the detached cells were suspended. A surface-treated titanium sample was placed in a well of a 48-well cell culture plate, and 500 μL of cell suspension was placed in the well so that the number of cells was 30,000 cells / well. The plates were placed in a CO2 incubator and cultured at 37 ° C. in a 5% CO2 atmosphere for 3 hours or 3 days, and cell proliferation was evaluated by the neutral red method and confocal laser scanning microscopy.

Analysis by the Neutral Red method shows that New-Ti treated with H (-) L (-), H (+) L (-), H (-) L (+), or H (+) L (+). Cell proliferation on Aged-Ti was evaluated. After a 3-day culture period, a titanium sample (cells adhered to the surface) was immersed in 300 μL α-MEM containing 150 μg / mL neutral red (Wako Pure Medicine) and cultured for 3 hours. The incorporated neutral red was extracted with a mixed solution of 50% ethanol and 1% acetic acid. The absorbance at 540 nm of the extract was measured using a plate reader (FilterMax F5, Molecular Devices). Measurements were performed using 6 samples in each group.

Confocal laser scanning microscopy evaluated cell proliferation on New-Ti and Aged-Ti treated with H (-) L (-) or H (+) L (+). After a culture period of 3 hours or 3 days, cells on a titanium sample were fixed with 4% paraformaldehyde and subjected to fluorescent staining. For fluorescent staining, cell nuclei and actin filaments were stained with 300 nM 4', 6-diamidino-2-phenylindole (DAPI; Thermo Fisher Scientific) and 165 nM rhodamine phalloidin (Thermo Fisher Scientific), respectively. Stained cells were observed using a confocal laser scanning microscope (TCS-SPE, Leica Microsystems), and stack images were acquired. The obtained image was analyzed by image analysis software Image J (National Institute of Health), and the cell coverage and the number of cells (number of cell nuclei) with respect to the observation field were calculated. Nine images were acquired in each group.
<Cell proliferation test results>

FIG. 12 (A) shows the results of proliferation (measurement by the neutral red method) of osteoblasts (MC3T3-E1 derived from mice) on the surface of newly produced titanium. Here, the vertical axis shows the neutral red value (% relative to the control value), and shows the experiment of the newly manufactured titanium. Radical treatment did not affect cell proliferation. FIG. 12B shows the proliferation of osteoblasts on the aged titanium surface. Here, the vertical axis shows the neutral red value (relative value% with respect to the control), and shows a comparative experiment between the newly manufactured titanium and the aged titanium. Although the proliferation of osteoblasts on the titanium surface decreased due to aging, cell proliferation equivalent to that of the new titanium surface was observed on the radically treated surface. Different alphabets indicate statistically significant differences between groups.

FIG. 13 (A) shows the proliferation (observation with a confocal laser scanning microscope) of osteoblasts (MC3T3-E1 derived from mice) on the surface of newly produced titanium. FIG. 13B shows the quantitative results of the cell coverage and the number of cells on the surface of the newly manufactured titanium. Here, the left figure on the vertical axis shows the coverage (%), and the right figure on the vertical axis shows the number of cells per image (number of cells). Radical treatment did not affect cell proliferation. FIG. 13 (C) shows the proliferation of osteoblasts (after 3 hours of culture) on the aged titanium surface. FIG. 13 (D) shows the proliferation of osteoblasts on the aged titanium surface (3 days after culture). FIG. 13 (E) shows the quantitative results of the cell coverage and the number of cells on the aged titanium surface. Here, the left figure on the vertical axis shows the coverage (%), and the right figure on the vertical axis shows the number of cells per image (number of cells). Although the proliferation of osteoblasts on the titanium surface decreased due to aging, cell proliferation equivalent to that of the new titanium surface was observed on the radically treated surface.

In FIGS. 13B and 13E, the different alphabets indicate statistically significant differences between the groups.
<Experiment 3>
<Contamination of titanium sample surface by bacterial biofilm>

Experiments were conducted using Aggregatibacter actinomycetemcomitans JCM 2434 (a type of causative agent of periodontal disease and peri-implantitis) provided by the Cellular Materials Development Office of RIKEN. Bacteria precultured in Brain Heart Infusion (BHI) liquid medium (Becton Dickinson Labware) containing 1% yeast extract (Oxoid, Hampshire) were suspended in sterile physiological saline and the concentration was approximately 5 × 108 colony forming units (CFU). ) / mL. The autoclaved New-Ti was placed in the wells of a 48-well cell culture plate and 1000 μL of BHI liquid medium containing 1% yeast extract and 100 μL of bacterial suspension were added. The plates were placed in an anaerobic jar, anaerobic using Aneropack (Mitsubishi Gas Chemical Company), and cultured in an incubator at 37 ° C for 48 hours (Biofilm-Ti). When the viable cell count in the biofilm formed after culturing was evaluated by the dilution plate method, the average was 5.12-log CFU per sample.
<Treatment of titanium samples contaminated with biofilm>

Assuming clinical treatment of peri-implantitis, the biofilm on the titanium surface was removed by ultrasonic scaling, and then various sterilization treatments were performed. Ultrasound scaling was performed using a miniMaster Piezon LED (EMS) and a PEEK plastic scaler chip (Peek tip straight, Star Chip). The output of the ultrasonic scaler was 70%, and the flow rate of the cooling water was 50 mL / min. The titanium sample was grasped with forceps and ultrasonic scaling was performed for 1 minute. The viable cell count after ultrasonic scaling was 2.16-log CFU on average per sample. H (-) L (-), H (+) L (-), H (-) L (+), H (+) L (+), H (+) L400 ( +), 0.2% chlorhexidine (CHX; Toyo Pharmaceutical Kasei) and 0.5% povidone iodine (PI; Meiji Seika Pharma) were treated for 5 minutes (each solution was used in 300 μL). H (+,-) and L (+,-) were set with the same settings as in "2. Surface treatment of titanium sample by hydrogen peroxide photolysis method" above. L400 (+) was performed using an LED with a wavelength of 400 nm.
<Experiment 4>
<Analysis of surface chemicals of biofilm-contaminated titanium samples>
FIG. 15 describes the effect of radical treatment on the surface of titanium contaminated with bacteria.
FIG. 15 shows the analysis results of the surface chemicals of the biofilm-contaminated titanium sample.

The chemical composition of the sample surface was analyzed by X-ray photoelectron spectroscopy. For analysis, New-Ti, ultrasonically scaled New-Ti, H (-) L (-), H (+) L (-), H (-) L (+) or H (+) L ( Biofilm-Ti treated with +) was used. XPS measurement was performed under the same conditions as in "3. Analysis of surface chemical substances" above. Measurements were performed using 3 samples in each group.
<Results of analysis experiment of surface chemicals of biofilm-contaminated titanium sample>

FIG. 14A shows the XPS analysis result of the titanium surface. Here, the vertical axis of each figure shows the intensity, and the unit is cps (count per second). cps means the intensity of photoelectrons captured by the detector per second. The horizontal axis of each figure shows the binding energy (eV). The titanium surface was contaminated by forming a biofilm of Aggregatibacter anctinomycestemcomtans (a type of causative agent of periodontitis and peri-implantitis), which was then subjected to ultrasonic scaling (US) and each treatment. FIG. 14B shows the result of quantitative analysis of carbon content based on the XPS spectrum. Here, the vertical axis shows the atomic percentage (%), and the horizontal axis shows the comparative experiment between the newly produced titanium and the titanium contaminated with bacteria. It was found that the carbon content on the titanium surface increases due to bacterial contamination, but the carbon content decreases due to radical treatment. In FIG. 14B, the different alphabets show statistically significant differences between the groups.
<Cell proliferation on the surface of titanium samples contaminated with biofilm>

FIGS. 15 and 16 describe the proliferation of osteoblasts on the surface of radically treated bacterially contaminated titanium. 15 and 16 show cell proliferation results on the surface of a titanium sample contaminated with biofilm.

Experiments were performed using MC3T3-E1 as in the "cell proliferation test" above. After culturing for 3 hours or 3 days, cell proliferation was evaluated by methyl thiazolyl tetrazorium (MTT) method, neutral red method and confocal laser scanning microscopy. In the MTT method, after New-Ti and ultrasonic scaling, H (-) L (-), H (+) L (-), H (-) L (+), H (+) L (+), H ( +) Biofilm-Ti treated with 400 L (+), CHX or PI for 5 minutes was tested. For H (+) L (+), Biofilm-Ti treated for 0, 1, 3, and 5 minutes was also used for cell proliferation analysis in order to investigate the effect of treatment time on subsequent cell proliferation. 300 μL of α-MEM containing 0.1% MTT (Tokyo Chemical Industry) was placed in the well of a 48-well cell culture plate, a titanium sample was immersed, and the cells were cultured in a CO2 incubator at 37 ° C. for 2 hours. After culturing, insoluble formazan produced by the reduction of MTT by cells was extracted with dimethyl sulfoxide. The absorbance at 595 nm of the extract was measured using a plate reader. Measurements were performed using 6 samples in each group.
In the neutral red method, H (-) L (-), H (+) L (-), H (-) L (+), H (+) L (+) after New-Ti and ultrasonic scaling 5 Biofilm-Ti treated for a minute was tested. The analysis was performed under the same conditions as in "5. Cell proliferation test" above.
For confocal laser scanning microscopy, we used New-Ti and Biofilm-Ti treated with H (-) L (-) or H (+) L (+) for 5 minutes after ultrasonic scaling. After a culture period of 3 hours or 3 days, cells on a titanium sample were fixed with 4% paraformaldehyde and subjected to fluorescent staining. In the image analysis of cell morphology, cell nuclei and actin filaments of cells cultured for 3 hours were stained with 300 nM DAPI (Thermo Fisher Scientific) and 165 nM rhodamine phalloidin (Thermo Fisher Scientific), respectively. In addition, for quantitative analysis of cell number, cell nuclei of cells cultured for 3 days were stained with 10 μM SYTO9 (Thermo Fisher Scientific). In this experiment, DAPI also stained biofilm-derived substances remaining on the surface of the titanium sample to increase the level of background noise, so SYTO9 was used in the quantitative analysis of cell numbers. Stained cells were observed using a confocal laser scanning microscope (TCS-SPE, Leica Microsystems), and stack images were acquired. The obtained image was analyzed by the image analysis software Image J (National Institute of Health), and the cell area, ferret diameter, peripheral length (image analysis of cell morphology) and cell number (quantitative analysis of cell number) were calculated. .. In the cell number analysis and cell morphology image analysis, 15 and 9 images were obtained for each group, respectively.
<Results of cell proliferation experiments on the surface of titanium samples contaminated with biofilm>

15 (A), (B), (C), (D), and (E) show the results of proliferation (measurement by the MTT method) of osteoblasts (MC3T3-E1 derived from mice) on the surface of bacterially contaminated titanium. Here, the vertical axis of each figure shows the MTT value (relative value% with respect to the control), and shows a comparative experiment between the newly produced titanium and the titanium contaminated with bacteria. FIG. 15A shows the results of radical treatment. "H (+) L (+)" increased cell proliferation. FIG. 15 (B) Povidone iodine (PI) and chlorhexidine (CHX) did not increase cell proliferation. PW is a treatment using pure water. FIG. 15C shows a case where radical treatment is performed by LEDs having different wavelengths. The effect of "H (+) 400L (+)" when the radical treatment was performed with a 400 nm LED was inferior to that of "H (+) L (+)" when the radical treatment was performed with a 365 nm LED. FIG. 15D shows a comparison of irradiation times. As is clear from FIG. 15 (D), the influence of radical treatment depended on the irradiation time. FIG. 15 (E) shows confirmation of the result of FIG. 15 (A) by the neutral red method. In FIG. 15, different alphabets indicate statistically significant differences between groups.

FIG. 16A shows the results of morphological observation (observation with a confocal laser scanning microscope) of osteoblasts (MC3T3-E1 derived from mice) on the surface of bacterially contaminated titanium. FIG. 17 (A) shows a morphological observation image of one cell and a cell nucleus on the surface of the newly manufactured titanium, FIG. 17 (B) shows the elongation of osteoblasts, and FIG. 17 (C) shows less elongation of osteoblasts. Indicates the state. FIG. 16B shows the quantitative results of parameters related to cell shape. Here, the left figure on the vertical axis shows the area (Area) (μm2), the intermediate figure on the vertical axis shows the Feret's diameter (μm), and the right figure on the vertical axis shows the perimeter (μm) around the cell. ) Is shown. The ferret diameter means the distance of the longest of the vertical or horizontal lengths of the rectangle circumscribing the extracellular diameter. The perimeter of the cell means the length around the outer diameter of the cell.
On the surface of bacterially contaminated titanium, cells were not stretched, but on the surface treated with radicals, cell stretch was observed. FIG. 16C shows the staining results of the number of osteoblasts on the surface of bacterially contaminated titanium 3 days after culturing. FIG. 16D shows the quantification result of the number of cells on the surface of bacterially contaminated titanium. Although the number of osteoblasts on the titanium surface decreased due to bacterial contamination, cell proliferation equivalent to that on the newly made titanium surface was observed on the radically treated surface.

In FIGS. 16B and 16D, the different alphabets indicate statistically significant differences between the groups.
<Experiment 5>
<Analysis experiment of hydroxyl radical generation>

FIG. 18 describes an analytical experiment for hydroxyl radical generation and experimental results. FIG. 18 shows the results of hydroxyl radical radical generation analysis.

Electron spin resonance analysis of hydroxyl radicals generated under the conditions of H (-) L (-), H (+) L (-), H (-) L (+) and H (+) L (+) It was measured by the (ESR) method. As the spin trapping agent, a water-soluble trapping agent called 5,5-dimethyl-1-pyrroline N-oxide (DMPO) applicable to molecular weight 113, O2-, HO, and C-center radical was used.
The experiment was conducted with 150 μL of hydrogen peroxide (H (+) condition) or pure water (H (-) condition) and 150 μL of 5,5-dimethyl-1-pyrroline N-oxide (DMPO; Labotec, Tokyo). , Japan) was mixed in the wells of a 48-well cell culture plate. The final concentrations of hydrogen peroxide and DMPO were 3% and 300 mM, respectively. Immerse the titanium disc in the prepared solution and irradiate it with an LED (irradiance: 1000 mW / cm2) with a wavelength of 365 nm for 15 seconds (L (+) condition) or hold it in a light-shielding box (L (-) condition). )did. The conditions of H (-) L (-), H (+) L (-) and H (-) L (+) were performed for 5 minutes in addition to the processing time of 15 seconds. Furthermore, in order to estimate the effect of the photocatalytic effect of titanium oxide formed on the titanium disk, under the conditions of H (-) L (+), hydroxyl radical generation analysis with and without immersion of the titanium disk was also performed. gone. ESR spectra were recorded using an X-band ESR spectrometer (JES-FA-100, JEOL, Tokyo, Japan). From the obtained spectrum, the concentration of DMPO-OH (hydroxyl radical trapped in DMPO) was calculated using dedicated software (Digital Data Processing, JEOL). Measurements were performed 3 times in each group.
<Summary>
<Results of analysis experiment of hydroxyl radical generation>

FIG. 18A is the result of hydroxyl radical generation analysis and shows the case where the treatment time is 15 seconds. FIG. 18B shows a case where the processing time is 5 minutes. When the treatment time was 15 seconds, DMPO-OH production of 81.6 μM was observed under the condition of H (+) L (+). On the other hand, under other conditions, DMPO-OH production was less than 0.2 μM. When the processing time is 5 minutes, the DMPO- is 0.10, 0.33 and 1.64 μM under the conditions of H (-) L (-), H (+) L (-) and H (-) L (+), respectively. OH production was observed. In addition, when the pure water was irradiated with LED without immersing the titanium disk (H (-) L (+) without Ti), the production of DMPO-OH was 0.72 μM. Therefore, the amount of hydroxyl radicals produced was larger when the titanium disc was immersed, suggesting that this increase is due to the photocatalytic action of titanium oxide.
<Conclusion>

From the results of these hydroxyl radical generation analysis experiments, the osteoblast proliferation effect of UV irradiation alone is limited, and if the treatment time is the same, it is significantly better to use UV radiation and UV irradiation together. It was found that it has a high proliferative effect.
As described above, the treatment of the implant surface for 1 to 5 minutes has a special effect that the osteoblasts can be restored to a state of good colonization and proliferation. Since the surface of the implant can be improved by short-time treatment in minutes, the colonization and proliferation of peri-implant osteoblasts can be improved.
<Embodiment 2>
<Limited to hydrogen peroxide solution>
<Outline of Embodiment 2>

Embodiment 2 does not contain additives (such as phenacetin and acetanilide) such as those contained in commercially available oxidol for the application of hydrogen peroxide solution used in an osteoblast colonization treatment apparatus on a metal material embedded in a body. Using hydrogen peroxide water, the numerical range such as the concentration of hydrogen peroxide water and the content of heavy metals of impurities is set.

The aqueous solution for cleaning by irradiation with ultraviolet rays and / or near-ultraviolet rays of the second embodiment has a hydrogen peroxide concentration of 1 w / v% or more and 7 w / v% or less, and a hydrogen peroxide stabilizer concentration of 81 ppm in the aqueous solution. It is characterized in that it contains only the following. If the concentration of hydrogen peroxide is 1 w / v% or less, hydroxyl radicals cannot be sufficiently generated and the sterilization work efficiency is poor. If the concentration of hydrogen peroxide is 7 w / v% or more, the amount of hydroxyl radicals generated becomes too large and a small amount of hydrogen peroxide stabilizer is used. It becomes difficult to maintain the quality and store it for about 1 to 2 days. Here, w / v% means how many grams of hydrogen peroxide is contained in 100 ml of the aqueous solution.

The ultraviolet and / and near-ultraviolet visible light irradiation cleaning aqueous solution of the second embodiment contains hydrogen peroxide, and this hydrogen peroxide is decomposed into hydroxyl radicals by ultraviolet rays and / and near-ultraviolet visible light irradiation, and the oral cavity Sterilize the periodontal disease bacteria inside. The bactericidal activity can be adjusted by the combination of the concentration of hydrogen peroxide and the intensity of light. For example, when the concentration of hydrogen peroxide is 3 w / v%, it is conceivable to irradiate with ultraviolet rays and / or near-ultraviolet visible light of about 405 nm (for example, a width of about plus or minus 10%). Here, reference is made to FIG. FIG. 20 is a conceptual diagram of the generation of hydroxyl radical, which is a sterilizer, by an aqueous solution for cleaning by irradiation with ultraviolet rays and / or near-ultraviolet visible light of the second embodiment.

When hydrogen peroxide (H2O2) before decomposition is irradiated with ultraviolet rays and / or near-ultraviolet visible light laser, it is photodecomposed as shown by the arrow and HO. Shows). This HO · has a structure having unpaired electrons, has strong oxidizing power, and sterilizes by oxidizing and destroying the cell membrane of the partner periodontal disease bacterium.

On the other hand, hydrogen peroxide solution has low stability and generally contains a stabilizer because hydrogen peroxide decomposes at the stage of distribution and storage. Stabilizers include phosphoric acid, phenacetin, acetanilide and the like, generally containing several hundred ppm. This is because these stabilizers have low reactivity by themselves and do not affect chemical reactions such as sterilization and bleaching involving hydrogen peroxide.

However, irradiation with ultraviolet rays and / or near-ultraviolet visible light laser is performed regardless of whether it is hydrogen peroxide or a stabilizer. Ultraviolet and / and near-ultraviolet visible light lasers have a strong ability to decompose chemical substances due to their high energy, and even stabilizers with generally low reactivity may be decomposed to produce unknown substances. In addition, hydroxy radicals generated by irradiating hydrogen peroxide with ultraviolet rays and / or near-ultraviolet visible light lasers also decompose stabilizers with their strong oxidizing power, and are unknown chemical substances due to unknown synthetic reactions between decomposition products. There is a risk of doing it.

Therefore, the following experiments were conducted to clarify the relationship between the concentration of the hydrogen peroxide stabilizer and the presence or absence of decomposition products.

That is, a hydrogen hydrogen solution A having a phenacetin concentration of 81 ppm as a stabilizer, a hydrogen hydrogen solution F having a phenacetin concentration of 334 ppm as a stabilizer, and a hydrogen hydrogen solution J having an acetanilide concentration of 177 ppm as a stabilizer. On the other hand, a laser beam having a wavelength of 405 nm was irradiated, and the presence or absence of a change in the HPLC chromatogram before and after the irradiation was evaluated.

FIG. 21 is a diagram showing the results of HPLC measurements on the aqueous solution A before laser irradiation. It has been shown to be free of substances other than the planned substances hydrogen peroxide and phenacetin. FIG. 22 is a diagram showing the results of HPLC measurement after irradiating the aqueous solution A with a laser for 5 minutes. As shown in FIGS. 21 and 22, no significant change was observed in the chromatogram after 5 minutes of laser irradiation. That is, no new substance has been confirmed in the hydrogen peroxide aqueous solution A having a phenacetin concentration of 81 ppm as a stabilizer by irradiation with a laser for 5 minutes. It should be noted that 5 minutes is the time for continuous laser irradiation in dental treatment such as periodontal disease for about several tens of seconds at the most, and if it is considered safe to continue laser irradiation for 5 minutes, the actual time is set. This is because it is considered that the safety in treatment is ensured.

FIG. 23 is a diagram showing the results of HPLC measurement of a hydrogen peroxide aqueous solution F having a phenacetin concentration as a stabilizer of 334 ppm before laser irradiation. Regarding the aqueous solution F, hydrogen peroxide and phenacetin are the only substances detected as contained substances before laser irradiation. FIG. 24 is a diagram showing the results of HPLC measurement after irradiating the aqueous solution F with a laser for 5 minutes. As shown in FIGS. 23 and 24, a new peak is generated in the chromatogram after 5 minutes of laser irradiation, and the generation of an unknown substance that was not present before the laser irradiation is hydrogen peroxide having a phenacetin concentration of 334 ppm as a stabilizer. It was found in the hydrogen peroxide solution F (arrow in FIG. 24).

FIG. 25 is a diagram showing the results of HPLC measurement of a hydrogen peroxide aqueous solution J having an acetanilide concentration as a stabilizer of 177 ppm before laser irradiation. As for the aqueous solution J, only hydrogen peroxide and acetanilide were detected before the laser irradiation. FIG. 26 is a diagram showing the results of HPLC measurement after irradiating the aqueous solution J with a laser for 5 minutes. As shown in FIGS. 25 and 26, a new peak was generated in the chromatogram after 5 minutes of laser irradiation, and an unknown substance that was not present before the laser irradiation in the hydrogen peroxide aqueous solution J having an acetanilide concentration of 177 ppm as a stabilizer. Generation of substances was observed (arrow in FIG. 26).

According to the above experiments, phenacetin and acetanilide, which are stabilizers contained in general hydrogen peroxide solution, are decomposed by laser irradiation for at least 5 minutes when the concentration is above a certain level, and decomposition products or compounds which are unknown substances are decomposed. Was shown to be generated. On the other hand, it was shown that if the phenacetin concentration was 81 ppm and the laser irradiation time was within 5 minutes, no decomposition product was produced.

When the treatment is performed using the ultraviolet and / and near-ultraviolet visible light irradiation cleaning aqueous solution of the second embodiment, the aqueous solution is always emitted, so that the hydrogen peroxide aqueous solution stays in a certain place and receives laser irradiation. There is no such thing. Therefore, if there is no change after 5 minutes of laser irradiation, it can be said that no new decomposition product is produced even when used clinically.
Therefore, it is desirable that the aqueous solution for cleaning by irradiating ultraviolet rays and / and near-ultraviolet rays of the present embodiment does not contain hydrogen peroxide stabilizer at all, but if it is contained, the concentration thereof is 81 ppm or less in this aqueous solution. be. The lower the concentration of the hydrogen peroxide stabilizer is, the more desirable it is from the viewpoint of the decomposition product of the reaction and the viewpoint of cost. As the hydrogen peroxide stabilizer, it is conceivable to use any one or more of phenacetin, acetanilide, and phosphoric acid.

The hydrogen peroxide stabilizer is added to prevent hydrogen peroxide from being decomposed by metal ions such as iron. Therefore, when iron and copper were analyzed in purified water used for diluting hydrogen peroxide, it was confirmed that both were below the detection limit (0.05 mg / L). Iron and copper are made by storing a stock solution of hydrogen peroxide solution containing less than a predetermined amount of stabilizer in a cool and dark place and diluting it to 3 w / v% with purified water. As a result of an accelerated test on those having a detection limit (0.05 mg / L) or less and a phenacetin and acetanilide content of 81 ppm (mg / L) or less, the result was obtained that the content was stable for 3 years at room temperature. ..
From the viewpoint of preventing the decomposition of hydrogen peroxide, it is desirable that the aqueous solution for cleaning by irradiation with ultraviolet rays and / or near-ultraviolet visible light of the second embodiment does not contain any impurity heavy metals. It was inspected by an apparatus having a detection limit of 0.05 mg / L whether the diluted hydrogen peroxide solution contained an impurity metal. As a result, neither iron nor copper was detected.

Therefore, even if hydrogen peroxide contains only 81 ppm or less of a stabilizer, if the content of iron or copper is 0.05 mg / L or less,

That is, if the stabilizer is contained in an amount of 81 ppm or less and the iron or copper content is 0.05 mg / L or less, an ultraviolet ray of about 405 nm (for example, a width of about plus or minus 10%) and / or a near-ultraviolet visible light irradiation laser is used. It can be an aqueous hydrogen peroxide solution that generates sufficient hydroxy radicals for the treatment of periodontal disease by irradiation.

When the ultraviolet and / and near-ultraviolet visible light irradiation cleaning aqueous solution of the second embodiment is used for cleaning teeth, for example, the ultraviolet and / and the near-ultraviolet visible light irradiation cleaning aqueous solution and the ultraviolet and / and near-ultraviolet visible light. A dental treatment device including a scaler chip that emits light and / or is configured, and cleaning is performed by simultaneously emitting ultraviolet rays and / and an aqueous solution for irradiation with near-ultraviolet visible light irradiation and ultraviolet rays / / and near-ultraviolet visible light from the tip of the scaler chip. It is possible.

In such a configuration, since metal ions promote the decomposition of hydrogen peroxide, it is desirable that the scaler chip has at least an ultraviolet ray and / or a non-metal surface on the inner surface of the flow path of the aqueous solution for cleaning by irradiation with near-ultraviolet visible light.

The concentration of the hydrogen peroxide solution is more preferably 2 w / v% or more and 6 w / v% or less, and most preferably about 3 w / v% or about 20%. This is because sufficient hydroxyl radicals are generated, and even a very small amount of stabilizer can maintain the quality for a sufficiently long time (about 3 years or more).

As described above, according to the first embodiment and the second embodiment, hydrogen peroxide, which is harmless even in the human body after implanting the implant, is supplied to the implant implanting portion, and UV irradiation by scattering and condensing is performed here. On the surface of the bone-implanted metal material in the body, a hydroxyl radical is generated to efficiently treat the surface of the implant member to improve osteoblast colonization and proliferation. Can be provided.

Claims (11)

A treatment device that improves the colonization and proliferation of osteoblasts in metal materials implanted in bone in the body.
One or more of ultraviolet rays, near-ultraviolet rays, and blue visible light (hereinafter referred to as "ultraviolet rays, etc.") to the hydrogen peroxide solution discharge port that discharges the hydrogen peroxide solution and the hydrogen peroxide solution supplied from the hydrogen peroxide solution discharge port. It is equipped with an irradiation port for ultraviolet rays, etc. that irradiates.)
On the internal bone-embedded metal material in which at least a part of the internal bone-embedded metal material is simultaneously irradiated with hydrogen peroxide solution and the above-mentioned ultraviolet rays, etc., on the surface of the exposed portion of the jawbone. Osteoblast colonization treatment device. The internal bone-embedded metal material according to claim 1, wherein the hydrogen peroxide solution discharge port and the ultraviolet irradiation port have a chip shape that can be inserted into a gap formed between the embedded metal material in the body and the bone. Upper osteoblast colonization treatment device. The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to claim 1 or 2, wherein the irradiation port for ultraviolet rays or the like is configured to scatter ultraviolet rays or the like. The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to any one of claims 1 to 3, wherein the irradiation port for ultraviolet rays and the like is configured to collect ultraviolet rays and the like. The osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material according to any one of claims 1 to 4, wherein the discharge rate of the hydrogen peroxide solution to be discharged is 100 CC / min or less. The osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material according to any one of claims 1 to 5, wherein the amount of ultraviolet rays or near-ultraviolet rays to be irradiated is 0.1 milliwatt or more. When the concentration of hydrogen peroxide is 1w / v% or more and 7w / v% or less,
The osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material according to any one of claims 1 to 6, wherein the concentration of the hydrogen peroxide stabilizer is 81 ppm (mg / L) or less in this aqueous solution. (Add 0 for hydrogen peroxide stabilizer)
When the concentration of hydrogen peroxide is 1w / v% or more and 7w / v% or less,
The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to claim 7, wherein the concentration of the hydrogen peroxide stabilizer is 0 ppm (mg / L) in this aqueous solution. The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to claim 7 or 8, wherein the concentration of hydrogen peroxide is 2 w / v% or more and 6 w / v% or less. The osteoblast colonization treatment apparatus on a metal material embedded in a bone in the body according to claim 7 or 9, wherein the hydrogen peroxide stabilizer is one or more of phenacetin and acetanilide. The osteoblast colonization treatment apparatus on an in-vivo bone-implanted metal material according to any one of claims 7 to 10, wherein the impurity heavy metal content is only 0.001 w / v% or less with respect to hydrogen peroxide.

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