Electrolyte for electrochemical decontamination and application thereof

Abstract

The invention relates to the field of surface cleaning of bacterial-infected bone implants, in particular to the field of stomatology, is used for cleaning biofilms and bacteria on the surfaces of dental implants or other infected parts, and provides an electrolyte for electrochemical decontamination and application of the electrolyte. The electrolyte for electrochemical decontamination is used for electrochemically removing bacteria and biological membranes around a bone implant, the electrolyte for electrochemical decontamination comprises iodized salt or a mixed solution of iodized salt and glycine, and the maximum concentration of the iodized salt and / or glycine is 10 mmol / L respectively. According to the invention, the oral implant or the bone implant is used as the anode, the biological membrane is removed by direct oxidation reaction, the method does not depend on the current electrochemical removal of bubble generation of the biological membrane, the complex surface of the implant can be more uniformly covered and cleaned, and the decontamination efficiency is improved; meanwhile, an efficient sterilization effect is provided, the effect of promoting osteogenesis is achieved, regeneration of surrounding bone tissue is helped, and the long-term stability and clinical effect of the implant are improved.

Description

Technical Field

[0001] The present invention relates to the field of cleaning the surface of bone implants infected by bacteria, in particular to the field of oral medicine, and is used for cleaning the biofilm and bacteria on the surface of oral dental implants or other infected parts, and in particular to an electrolyte for electrochemical decontamination and its application in electrochemical removal of bacteria and biofilm on oral implants. Background Art

[0002] With the continuous development and popularization of oral implant technology, more and more patients choose dental implants as a replacement solution for missing teeth. However, peri-implantitis and poor implant osseointegration are still the main problems that need to be solved in clinical practice. These problems not only affect the long-term stability of implants, but may also lead to implant failure, causing pain and financial burden to patients.

[0003] During the implantation process or due to poor hygiene habits after surgery, implants may be contaminated by various bacteria and biofilms. These contaminants can trigger an inflammatory response, leading to bone loss around the implant, and affecting the stability and function of the implant. At present, implant surface decontamination mainly adopts mechanical removal, chemical cleaning and laser treatment. However, these methods have the following limitations: 1. Mechanical decontamination may damage the implant surface and affect its microstructure and function; 2. The decontamination effect of chemical decontamination is unstable, and harmful substances may remain; 3. Laser decontamination equipment is expensive, complicated to operate, and difficult to promote. Therefore, electrochemical decontamination technology has received widespread attention in the medical field in recent years. This technology can efficiently remove biofilms and contaminants on the implant surface through the action of electrolyte and electric field, avoiding mechanical damage; at the same time, its electrolyte composition is controllable, which can reduce the harmful residues of chemical detergents; in addition, it can not only remove contamination, but also improve the microenvironment around the implant by adjusting the electrolyte composition.

[0004] However, the popular Galvosurge products on the market mainly use the physical effect of generating hydrogen bubbles to peel off and remove biofilm. Due to the low efficiency of gas generation, the electrolysis process requires high energy consumption, and it is difficult to ensure a uniform and stable decontamination effect. Summary of the invention

[0005] Based on the above background, the present invention provides an electrolyte for electrochemical decontamination and its application. By improving the electrolyte composition and optimizing the mechanism of removing biofilm, it not only provides a highly efficient bactericidal effect, but also has the effect of promoting osteogenesis, helping the regeneration of surrounding bone tissue, and improving the long-term stability and clinical effect of the implant.

[0006] To achieve the above object, the technical solution of the present invention is:

[0007] An electrolyte for electrochemical decontamination is used for electrochemically removing bacteria and biofilm around bone implants, characterized in that it includes iodized salt or a mixture of iodized salt and glycine, and the maximum concentration of the iodized salt and / or glycine is 10 mmol / L respectively.

[0008] Preferably, the iodide salt is sodium iodide, potassium iodide or calcium iodide.

[0009] Preferably, the electrolyte is any one of a mixture of potassium iodide and sodium iodide, a mixture of sodium iodide and calcium iodide, a mixture of calcium iodide and potassium iodide, a calcium iodide solution, or a mixture of calcium iodide and glycine.

[0010] Preferably, the electrolyte is a mixture of calcium iodide and glycine.

[0011] The present invention also provides the use of the electrolyte in electrochemically removing bacteria and biofilm from oral implants, using the implant as an anode and utilizing an oxidation reaction to decompose the biofilm, and has the ability to promote bone formation.

[0012] Preferably, the maximum current in the electrochemical process is less than 10 mA.

[0013] Preferably, the maximum voltage during the electrochemical process is 5V.

[0014] Preferably, the voltage in the electrochemical process is 3-5V, and the electrochemical treatment time is 1-5min.

[0015] Preferably, the voltage in the electrochemical process is 3V and the electrochemical treatment time is 3-5min.

[0016] Preferably, the electrolyte is a mixture of potassium iodide and glycine, the voltage in the electrochemical process is 3V, and the electrochemical treatment time is 1 min.

[0017] Due to the adoption of the above technical solution, the present invention has the following advantages and positive effects compared with the prior art:

[0018] The electrochemical electrolyte provided by the present invention mainly includes iodized salt or a mixture of iodized salt and glycine. It uses an oral implant or a bone implant as an anode and utilizes a direct oxidation reaction to remove biofilm. It does not rely on the bubble generation of the current electrochemical biofilm removal, and can more evenly cover and clean the complex surface of the implant, thereby improving the decontamination efficiency. At the same time, it provides a highly efficient bactericidal effect, and also has the function of promoting osteogenesis, helping the regeneration of surrounding bone tissue, and improving the long-term stability and clinical effect of the implant. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1This is a graph of cell proliferation activity after culturing rBMSCs (rat bone marrow mesenchymal stem cells) using electrolytes with different components in a concentration gradient in Example 1 of the present invention, wherein (a) is rBMSCs cultured in the electrolyte for one day; (b) is rBMSCs cultured in the electrolyte for three days.

[0020] Figure 2 The curve of current variation with time when the voltage is constant during the electrochemical decontamination process with different electrolyte compositions in Example 1 of the present invention;

[0021] Figure 3 The sterilization conditions of the electrochemical decontamination process with different electrolyte compositions and different voltages in Example 1 of the present invention are shown. The bacteria on the surface of the titanium sheet are fluorescently stained. Green fluorescence represents live bacteria, and red fluorescence represents dead bacteria. AP is a commonly used sterilization method in clinical practice.

[0022] Figure 4 The sterilization conditions during the electrochemical decontamination process with different electrolyte compositions and different voltages in Example 1 of the present invention are shown. Bacteria are coated on the surface of the titanium sheet to observe the residual bacteria on the titanium sheet.

[0023] Figure 5 The sterilization conditions during different electrolyte compositions, 3V voltage, and different electrochemical decontamination times in Example 1 of the present invention;

[0024] Figure 6 The sterilization conditions during different electrolyte compositions, 1V voltage, and different electrochemical decontamination times in Example 1 of the present invention;

[0025] Figure 7 Rat bone marrow mesenchymal stem cells (rBMSCs) were cultured on the surface of the titanium sheet after electrochemical decontamination with different electrolyte compositions according to Example 1 of the present invention, and the alkaline phosphatase (ALP) activity was measured after 7 days of osteogenic induction. DETAILED DESCRIPTION

[0026] The following is a further detailed description of an electrochemical sterilization electrolyte and its application proposed by the present invention in conjunction with the accompanying drawings and specific embodiments. The advantages and features of the present invention will become more apparent from the following description.

[0027] Example 1

[0028] In this embodiment, electrolytes with different concentration gradients and different components are prepared, which are mainly listed in the following Table 1:

[0029] Table 1

[0030] Element NaI+KI <![CDATA[NaI+CaI2]]> <![CDATA[KI+CaI2]]> <![CDATA[CaI2]]> <![CDATA[CaI2 + Glycine]]> Blank control group 0 0 0 0 0 Experimental Group 1 10 10 10 10 10 Experimental Group 2 100 100 100 100 100 Experimental Group 3 1000 1000 1000 1000 1000

[0031] Note: The concentrations in the table refer to the concentration of each component. For example, the concentration of NaI+KI group is 10mmol / L, which means the concentrations of NaI and KI are 10mmol / L respectively.

[0032] 1. Cell proliferation / toxicity assay

[0033] rBMSCs (rat bone marrow mesenchymal stem cells) were cultured using electrolytes of different gradient concentrations and different components in Table 1, and the cell proliferation activity was detected after one and three days of culture. The results of the cell activity detection were Figure 1 Shown in Figure 1 It can be seen that the proliferation activity of rBMSCs cells cultured with the five electrolyte components at a concentration of 10mmol / L is higher than that of cells cultured with electrolytes at concentrations of 0mmol / L (blank control group), 100mmol / L, and 1000mmol / L. This indicates that under the experimental conditions, the five electrolyte components at a concentration of 10mmol / L did not show obvious cytotoxicity, and this concentration showed the best cell compatibility in this experiment.

[0034] 2. Safety during electrochemical decontamination

[0035] Electrochemical decontamination was performed on the electrolytes of different components in experimental group 1. The classic three-electrode system was used, with titanium sheet as anode, platinum electrode as counter electrode, saturated potassium nitrate solution as reference electrode, and voltages set at 1V, 3V, and 5V. The current changed with time during the treatment with different voltages. The maximum current recorded during the decontamination process of different electrolyte components was less than 10mA. The results are shown in the attached figure. Figure 2 As shown, from Figure 2 It can be seen that the electrochemical decontamination process is safe.

[0036] 3. Verify the sterilization effect

[0037] The surface of the titanium sheet was coated with six bacteria commonly found in peri-implantitis, including Aggregatibacteractinomycetemcomitans (Aa), Actinomyces naeslundii (An), Streptococcus mutans (Sm), Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn) and Veillonella parvula (Vp). The bacteria were fluorescently stained, with green fluorescence representing live bacteria and red fluorescence representing dead bacteria. Electrochemical decontamination and sterilization were performed using electrolytes of different compositions in experimental group 1 in Table 1. The electrochemical treatment time was 1 min, and the voltages during the electrochemical process were kept constant at 1 V, 2 V, and 3 V, respectively. The results are shown in FIG. Figure 3 As shown, PC is the live bacteria on the titanium sheet before treatment, and the AP experimental group is the air sandblasting method commonly used in clinical sterilization (AP in the following experimental groups is air sandblasting treatment). This technology can also be used to remove biofilm around implants during implant maintenance. Photos of bacteria residues on the surface of the titanium sheet after 1min, 2min, and 3min of treatment. From the results, it can be seen that the calcium iodide and glycine groups achieved a good sterilization effect at 1V-1min, and the sterilization effect was better than AP-1min; at 3V-1min and 5V-1min, all groups achieved a good sterilization effect, and the sterilization effect was better than AP-3min and AP-5min. It shows that the above method shortens the treatment time compared with the current commonly used clinical methods, and has a good sterilization effect. Moreover, the calcium iodide and glycine groups can use low voltage to achieve a good sterilization effect at the same electrochemical treatment time compared with other groups.

[0038] 4. Verify the sterilization effect

[0039] (1) Six kinds of mixed bacteria, Aa, An, Sm, Pg, Fn, and Vp, were coated on a titanium sheet. Different electrolytes in experimental group 1 were used. Voltages of 1 V, 3 V, and 5 V were used for 1 min of electrochemical decontamination. The residual bacteria on the surface of the titanium sheet were observed. The results are as follows: Figure 4 As shown, PC is the bacteria on the untreated titanium sheet. Figure 4 It can be observed that there are no residual bacteria on the surface of the calcium iodide and glycine groups at 3V-1min, and at 5V-1min, there are no residual bacteria in all electrolyte groups. It can be concluded that the calcium iodide and glycine groups can achieve better sterilization effects at low voltages compared to other groups at the same electrochemical treatment time, and the minimum voltage parameter suitable for electrochemical decontamination is preliminarily screened to be 3V.

[0040] (2) Another batch of mixed bacteria was coated on the titanium sheet. Different electrolytes in Experimental Group 1 were used. A constant voltage of 3 V was used for 3 min and 5 min of electrochemical decontamination. The residual bacteria on the surface of the titanium sheet were observed. The results were as follows: Figure 5 As shown in the figure, PC is the bacteria on the untreated titanium sheet, and the AP experimental group is the air sandblasting sterilization method commonly used in clinical practice. The residual bacteria on the titanium sheet surface after 1 minute of treatment can be observed from the figure. After 3V-3min / 5min treatment, there is no residual bacteria on the surface of all electrolyte groups. Figure 4 and Figure 5Comparison shows that the appropriate voltage and time parameters for electrochemical decontamination of potassium iodide and sodium iodide, sodium iodide and calcium iodide, potassium iodide and potassium iodide, and calcium iodide electrolytes are 3V, 3-5min, respectively; while the appropriate voltage and time parameters for electrochemical decontamination of calcium iodide and glycine electrolytes are 3V, 1min, respectively.

[0041] 5. Crystal violet staining results

[0042] Another batch of mixed bacteria was coated on the titanium sheet. Different electrolytes in experimental group 1 were used. After electrochemical decontamination was performed at a voltage of 1 V for 1 min, 3 min, and 5 min, the crystal violet staining quantitative results of the residual bacteria on the titanium sheet surface were observed. The results are as follows: Figure 6 As shown in the figure, it can be observed that under low voltage, after 1V-1min / 3min / 5min treatment, only the calcium iodide and glycine groups can achieve better bactericidal effects compared with the control group, and the other groups have little difference.

[0043] 6. Osteogenesis

[0044] The titanium sheet was treated with electrochemical decontamination using electrolytes of different components in experimental group 1 at a voltage of 3V-3min, and AP was also used to treat the titanium sheet. Rat bone marrow mesenchymal stem cells (rBMSCs) were cultured on the surface of the treated titanium sheet and osteogenic induction was performed for 7 days. The alkaline phosphatase (ALP) activity on the surface of the titanium material treated with different electrolytes was observed. The results are as follows Figure 7 As shown in the figure, it can be seen that compared with the blank control group, the titanium surfaces after decontamination in the sodium iodide and potassium iodide, sodium iodide and calcium iodide, potassium iodide and calcium iodide, calcium iodide, calcium iodide and glycine groups all have good osteogenic properties, among which the calcium iodide and glycine group has the most significant bone promoting effect.

[0045] Through the above verification, the electrolyte provided by the present invention can not only remove biofilm, but also has the effect of promoting bone tissue regeneration, providing a dual function of antibacterial and osteogenesis. In particular, the electrolyte containing calcium iodide and glycine can achieve the effects of sterilization and biofilm removal at a lower voltage and a shorter treatment time, and the effect of promoting bone tissue regeneration is most significant.

[0046] The embodiments of the present invention are described in detail above in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments. Even if various changes are made to the present invention, if these changes fall within the scope of the claims of the present invention and their equivalents, they still fall within the protection scope of the present invention.

Claims

1. An electrochemical decontamination electrolyte for electrochemically removing bacteria and biofilm around bone implants, characterized in that: It comprises iodized salt or a mixed solution of iodized salt and glycine, wherein the maximum concentration of the iodized salt and / or glycine is 10 mmol / L respectively.

2. The electrochemical decontamination electrolyte according to claim 1, characterized in that: The iodized salt is sodium iodide, potassium iodide or calcium iodide.

3. The electrochemical decontamination electrolyte according to claim 1 or 2, characterized in that: The electrolyte is any one of a mixture of potassium iodide and sodium iodide, a mixture of sodium iodide and calcium iodide, a mixture of calcium iodide and potassium iodide, a calcium iodide solution, or a mixture of calcium iodide and glycine.

4. The electrochemical decontamination electrolyte according to claim 3, characterized in that: The electrolyte is a mixture of calcium iodide and glycine.

5. Use of the electrolyte according to any one of claims 1 to 4 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The implant is used as an anode, and an oxidation reaction is utilized to decompose the biofilm, and the implant has a bactericidal effect and an osteogenesis-promoting property.

6. Use of the electrolyte according to claim 5 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The maximum current in the electrochemical process is less than 10 mA.

7. Use of the electrolyte according to claim 5 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The maximum voltage during the electrochemical process is 5V.

8. Use of the electrolyte according to claim 7 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The voltage in the electrochemical process is 3-5V, and the electrochemical treatment time is 1-5min.

9. Use of the electrolyte according to claim 8 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The voltage in the electrochemical process is 3V, and the electrochemical treatment time is 3-5min.

10. Use of the electrolyte according to claim 8 in electrochemical removal of oral implant bacteria and biofilm, characterized in that: The electrolyte is a mixture of potassium iodide and glycine, the voltage during the electrochemical process is 3V, and the electrochemical treatment time is 1 minute.

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