Powder composition

Abstract

To provide a powder composition allowing both therapy and prophylaxis of peri-implantitis.SOLUTION: A powder composition for air polishing within an oral cavity, the composition comprising a carrier including an antibacterial agent supported on a dental abrasive as a support. The dental abrasive is preferably a calcium-containing abrasive. The antibacterial agent is preferably a cationic antibacterial agent. The carrier preferably has a supported amount of the antibacterial agent of 0.008 mg / g or more.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a powder composition. [Background technology]

[0002] Dental implant treatment is usually performed by placing a metal implant in the jawbone and attaching an artificial dental crown on top of it. Depending on the prognosis management situation after implant surgery, the area around the implant may become infected with bacteria, causing peri-implantitis. If peri-implantitis progresses, it can cause the implant to fall out, so preventative and treatment methods are being investigated.

[0003] One method for treating peri-implantitis is the air abrasion method, in which abrasive powder is sprayed using air as a medium. For example, Patent Document 1 discloses a blast abrasive for treating peri-implantitis using the air abrasion method. The abrasive disclosed in Patent Document 1 contains a calcium phosphate compound material and hydroxyapatite. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-198355 Summary of the Invention [Problem to be solved by the invention]

[0005] One of the initial treatments for peri-implantitis is to remove the biofilm that has formed on the implant surface. This can be achieved, for example, by spraying an abrasive onto the surface using air abrasion. However, there is a need for dental abrasives that can inhibit the formation of biofilm, a bacterial membrane.

[0006] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a powder composition that can treat and even prevent peri-implantitis. [Means for solving the problem]

[0007] [1] A powder composition for air polishing the oral cavity, comprising a carrier in which an agent having antibacterial properties is supported on a dental abrasive as a carrier. [2] The powder composition according to [1], wherein the dental abrasive is a calcium-containing abrasive. [3] The powder composition according to [1] or [2], wherein the dental abrasive is a calcium phosphate compound. [4] The powder composition according to any one of [1] to [3], wherein the agent having antibacterial properties is a cationic antibacterial agent. [5] The powder composition according to any one of [1] to [4], wherein the amount of the agent having antibacterial properties carried by the carrier is 0.008 mg / g or more. [Effects of the Invention]

[0008] According to the present invention, a powder composition capable of treating and even preventing peri-implantitis can be provided. [Brief explanation of the drawings]

[0009] [Figure 1] The adsorption isotherm is plotted with the concentration of chlorhexidine gluconate (CHG) (mg·dm-3) on the horizontal axis and the amount of CHG adsorbed (mg·g-1) on the vertical axis. [Figure 2] 2 is a graph obtained by fitting the adsorption isotherm shown in FIG. 1 to the Freundlich adsorption equation. [Figure 3] FIG. 1 shows the powder X-ray diffraction (XRD) profile of the powder composition. [Figure 4] FIG. 1 shows the sustained release amount of CHG. [Figure 5] FIG. 1 shows the sustained release amount of CHG. DETAILED DESCRIPTION OF THE INVENTION

[0010] <Powder composition> The present invention is a powder composition for air abrading the oral cavity. Air abrasion is a type of jet cutting using so-called air abrasion. Air abrasion is a procedure that removes deposits from tooth or implant surfaces by impacting them with a mixture of compressed air and powder. One aspect of the present invention is cutting powder for use in air ablation.

[0011] The powder composition of this embodiment contains a carrier in which an agent having antibacterial properties is supported on a dental abrasive as a carrier. Hereinafter, "agent having antibacterial properties" may be abbreviated to "antibacterial agent" and "dental abrasive" may be abbreviated to "abrasive."

[0012] In one embodiment of the present invention, a drug having a positive surface potential and a dental abrasive having a negative surface charge are adsorbed onto the carrier by electrostatic interaction.

[0013] Peri-implantitis is caused by a bacterial biofilm that forms on the surface of teeth and implants. Destruction and removal of biofilms is effective in treating peri-implantitis, while inhibiting biofilm formation is effective in preventing it.

[0014] The carrier contained in the powder composition of this embodiment comprises an abrasive capable of destroying biofilms and an antibacterial agent capable of inhibiting biofilm formation. By colliding the carrier with compressed air against the tooth surface or implant surface, the abrasive agent cuts the biofilm and the antibacterial agent is delivered locally. This allows for the destruction of biofilms and the application of the antibacterial agent simultaneously.

[0015] In addition, biofilms tend to be negatively charged, and the surface of implants may also be negatively charged. When cationic antibacterial agents are used as antibacterial agents, they electrostatically adsorb to the negatively charged biofilms and implant surfaces, and can exert their antibacterial effects for a specific period of time.

[0016] By using an antibacterial agent as a carrier supported on an abrasive, the antibacterial agent is less likely to scatter during air abrasion, making it easier to deliver the antibacterial agent locally to the desired location.

[0017] The powder composition of this embodiment can treat and prevent peri-implant infections such as peri-implantitis, as well as gingivitis, periodontitis, and periodontal diseases including peri-implant mucositis.

[0018] (Antibacterial drugs) Any antibacterial agent used in dentistry can be used, and for example, one or more selected from cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, dequalinium chloride, domiphen bromide, chlorhexidine hydrochloride, chlorhexidine gluconate, chlorhexidine sodium gluconate, bisabolol chlorhexidine, lactoferrin, etc. can be used as appropriate.

[0019] The antibacterial agent is preferably a cationic antibacterial agent, and the cationic antibacterial agent is preferably one or more selected from cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, domiphen bromide, chlorhexidine hydrochloride, and chlorhexidine gluconate.

[0020] (abrasive) The abrasive may be any abrasive used in dentistry, such as calcium-containing abrasives and silica. In this embodiment, calcium-containing abrasives are preferred, and one or more selected from calcium carbonate, dicalcium phosphate, tricalcium phosphate, calcium orthophosphate, calcium metaphosphate, calcium polyphosphate, calcium oxyapatite, sodium carbonate, and sodium bicarbonate are preferred.

[0021] The abrasive is preferably a calcium phosphate compound, and the calcium phosphate is preferably one or more selected from α-tricalcium phosphate, β-tricalcium phosphate, and tetracalcium phosphate.

[0022] (loading amount) The support preferably has an antimicrobial drug loading of 0.008 mg / g or more, more preferably 0.010 mg / g or more, and even more preferably 0.015 mg / g or more. When the amount of the antibacterial agent supported is equal to or greater than the lower limit, high antibacterial activity can be exhibited.

[0023] The amount of the antimicrobial agent carried can be measured either by a method of calculating it from the amount charged, or by a method of calculating it by analyzing the powder composition.

[0024] [Calculation method based on the amount of ingredients] First, an aqueous solution containing an antibacterial agent and a powdered abrasive are stirred, and after preparing the powder, the mixture is transferred to a centrifuge tube and centrifuged for solid-liquid separation. The concentration is then determined by measuring the absorbance of the supernatant solution. The amount of antibacterial agent supported on the abrasive is calculated by subtracting the concentration determined by the absorbance from the concentration of the antibacterial agent in the prepared "antibacterial agent-containing aqueous solution."

[0025] [Method for calculating by analyzing powder composition] First, the powder composition is immersed in a weak acidic solution to dissolve the surface of the abrasive that constitutes the powder composition, thereby releasing the supported antibacterial agent into the weak acidic solution. The amount of antibacterial agent released can then be determined by measuring the absorbance of the weakly acidic solution into which the antibacterial agent has been released. Dilute hydrochloric acid can be used as the weakly acidic solution.

[0026] The powder composition of this embodiment may be a powder composition consisting of the above-mentioned support, or may contain the support as the main component and other optional components within a range that does not impair the effects of the present invention.

[0027] <Method for producing powder composition> The support contained in the powder composition can be produced by preparing an antibacterial aqueous solution containing the antibacterial agent, adding an abrasive to the antibacterial aqueous solution, and stirring the mixture. Specifically, the antibacterial agent molecules in the antibacterial aqueous solution are adsorbed onto the abrasive.

[0028] The higher the concentration of the antibacterial agent in the aqueous antibacterial solution, the greater the amount of the antibacterial agent supported. For this reason, it is preferable to prepare an aqueous antibacterial solution with an antibacterial agent concentration of 5 ppm to 1000 ppm, preferably 30 ppm to 500 ppm.

[0029] The amount of abrasive added to the antibacterial aqueous solution is preferably 40% by mass to 60% by mass relative to the total amount of the antibacterial aqueous solution, from the viewpoint of adsorbing the antibacterial agent and the abrasive through electrostatic interaction.

[0030] As for the stirring conditions when adding an abrasive to an antibacterial aqueous solution and stirring, it is preferable to adjust the rotation speed in the range of 500 ppm to 1000 ppm.

[0031] After the stirring step, the mixture is centrifuged to remove the supernatant, and then freeze-dried to obtain a powder composition containing a carrier in which the antibacterial agent is supported on an abrasive carrier. [Example]

[0032] The present invention will be described in more detail below with reference to specific examples, although the present invention is not limited to the examples shown below.

[0033] <Preparation of Powder Composition> Chlorhexidine gluconate solution (20%) (manufactured by Nichi-Iko Pharmaceutical Co., Ltd.) was used as the antibacterial agent, and β-tricalcium phosphate (β powder, manufactured by Brainbase Co., Ltd., average particle size 45 μm) was used as the dental abrasive. Hereinafter, chlorhexidine gluconate solution (20%) will be referred to as "CHG" and β-tricalcium phosphate as "β-TCP."

[0034] 3 g of β-TCP was added to 3 ml of CHG solution diluted to a predetermined concentration, and the mixture was stirred for 0.5 hours at 24° C. The rotation speed during stirring was set to 800 rpm. Here, the "predetermined concentrations" are 10 ppm, 50 ppm, 100 ppm, 300 ppm, and 500 ppm.

[0035] The mixture was then centrifuged at 9000 rpm for 8 minutes, the supernatant was removed, and the mixture was freeze-dried at −80° C. for 24 hours to obtain a powder composition.

[0036] The horizontal axis shows the CHG concentration (mg dm -3 ), and the vertical axis shows the amount of CHG adsorbed (q / mg g -1 ) is plotted in Figure 1. When the adsorption isotherm shown in Figure 1 was fitted to the Freundlich adsorption equation, a high correlation coefficient was obtained, as shown in Figure 2. This confirmed that CHG was supported on β-TCP by chemical adsorption, which fits the Freundlich adsorption equation.

[0037] Figure 3 shows the XRD profile of the powder composition. (XRD profile measurement conditions) Measuring equipment: Rigaku MiniFlex ·Radiation source:CuKα Measurement range (2θ): 4°~50° Scan speed: 4° / min Sampling: 0.04° Voltage 30kV, current 15mA

[0038] In Figure 3, the numbers in parentheses for "β-TCP / CHG()" indicate the dilution concentration of the CHG solution. For example, "β-TCP / CHG(500)" refers to a powder composition obtained by adding β-TCP to a CHG solution diluted to 500 ppm. "β-TCP" refers to the XRD results of β-TCP alone.

[0039] As shown in Figure 3, it was confirmed that the crystalline structure of β-TCP was maintained when CHG was supported.

[0040] The amount of CHG supported was measured by the following method. First, an aqueous solution containing CHG (3 mL) and TCP powder (3 g) were stirred. After the powder was prepared, it was transferred to a 15 mL centrifuge tube and centrifuged (9000 rpm, 8 minutes) for solid-liquid separation. The absorbance (230 nm) of the supernatant solution was then measured to determine the concentration. The amount of CHG supported on the TCP powder was calculated by subtracting the concentration determined by absorbance from the CHG concentration in the "aqueous solution containing CHG" that was used.

[0041] Table 1 shows the amount of CHG supported (units: ppm and mg g) for each dilution concentration of CHG solution. -1 ) is shown.

[0042] [Table 1]

[0043] As shown in Table 1, it was confirmed that the higher the concentration of the CHG solution, the greater the amount of CHG supported.

[0044] <Sustained release test> The sustained release amount of CHG for the powder compositions of Examples 1 and 3 to 6 was measured. 0.3 g of each powder composition was placed on a 10 cm 3 The test was carried out at 37°C, and 10 ml of the solution was collected at each time point (0.3, 0.5, 1, 3, 4, 8, 24, 48, and 72 hours), and the same amount of saline at the same temperature was immediately added. The amount of CHG released was determined by measuring the absorbance at a wavelength of 230 nm using a spectrophotometer by ultraviolet absorption.

[0045] The results are shown in Figures 4 and 5. In Figures 4 and 5, the number n is 3. As shown in Figures 4 and 5, the total sustained release amount depended on the concentration of CHG.

[0046] <Antibacterial evaluation against Staphylococcus aureus and Escherichia coli> 0.5 g of each of the powder compositions of Examples 1 to 6 and Comparative Example 1 was added to LB liquid medium and shaken at 37° C. for 24 hours, followed by centrifugation at 9000 rpm for 10 minutes, and the supernatant was extracted to obtain an extract. 4.9cm 3 0.1cm 3 Bacterial solution 1 and bacterial solution 2 were inoculated and cultured at 37°C for 24 hours with shaking. After that, the absorbance at a wavelength of 600 nm was measured using a spectrophotometer. The absorbance value is proportional to the turbidity of the culture solution, so the viable cell count (growth value) was measured using this value.

[0047] Bacterial solution 1 contains Staphylococcus aureus, a gram-positive bacterium (number of bacteria: 1 × 10 5 CFU / tube). Bacterial solution 2 contains Escherichia coli (bacterial count: 1 x 10 5 CFU / tube).

[0048] The antibacterial activity value (R) was calculated from the obtained viable cell count (growth value) using the following formula described in JIS Z 2801. R=UA (U is the average common logarithm of the viable cell count (growth value) after 24 hours for the control, and A is the average common logarithm of the viable cell count (growth value) after 24 hours for the sample).

[0049] The higher the value of R obtained from the above formula, the higher the antibacterial activity, and it is particularly preferable that R is 2.0 or more.

[0050] Table 2 below shows the results when bacterial solution 1 (Staphylococcus aureus) was used, and Table 3 shows the results when bacterial solution 2 (Escherichia coli) was used.

[0051] [Table 2]

[0052] [Table 3]

[0053] As shown in Tables 2 and 3, it was confirmed that the support in which CHG was supported on β-TCP exhibited higher antibacterial activity than β-TCP alone. In particular, it was confirmed that Examples 3 to 6 exhibited antibacterial activity of 2.0 or more against Staphylococcus aureus, and Examples 4 to 6 exhibited antibacterial activity of 2.0 or more against Escherichia coli.

[0054] <Antibacterial activity against Streptococcus mutans> The antibacterial activity against Streptococcus mutans was evaluated in the same manner as in the above <Evaluation of antibacterial activity against Staphylococcus aureus and Escherichia coli>, except that BHI medium was used and bacterial solution 3 was used as the bacterial solution. Bacterial solution 3 contains Streptococcus mutans (number of bacteria: 4 x 10 5 CFU / tube).

[0055] Table 4 below shows the results when bacterial solution 3 (Streptococcus mutans) was used.

[0056] [Table 4]

[0057] As shown in Table 4, it was confirmed that the support in which CHG was supported on β-TCP exhibited higher antibacterial activity than β-TCP alone. In particular, it was confirmed that Examples 3 to 6 exhibited antibacterial activity of 2.0 or more against Streptococcus mutans.

[0058] <Evaluation of residual biofilm amount> [Preparation of hydroxyapatite ceramics] 0.50 g of hydroxyapatite (HAP-100, manufactured by Taihei Chemical Industry Co., Ltd., surface potential: -20.73 mV) was uniaxially pressed at a molding pressure of 50 MPa to form a coin shape with a diameter of approximately 11 mm and a thickness of approximately 1.6 mm. The mixture was then fired in a steam atmosphere at 1200°C for 5 hours to obtain a sintered ceramic body. The heating rate during firing was 5°C min -1 The relative density of the obtained ceramics was 96.9%.

[0059] [Biofilm formation] Streptococcus mutans (number of bacteria: 4 x 10 5 CFU / tube) were pre-cultured under anaerobic conditions at 37°C for 22 hours. After that, the medium was replaced with 2x BHI medium, and the bacterial count was increased to 2 x 10 6 The bacterial solution was adjusted to a ratio of bacterial solution:sterilized water:10% sucrose solution = 5:4:1, and the bacterial solution and ceramics were placed in a 24-well plate. After that, the plate was cultured under anaerobic conditions at 37°C for 24 hours, and a biofilm was formed on the ceramic surface.

[0060] [Evaluation of remaining biofilm] The ceramics with biofilms formed on their surfaces were transferred to a 6-well plate, and suspensions 1 to 6 listed in Table 5 were dropped onto the ceramics, followed by standing at 37°C for 24 hours. After standing, the ceramics were washed with phosphate-buffered saline (PBS) and stained with crystal violet. After staining for 15 minutes at room temperature, the ceramics were washed with PBS, and the dye was extracted with 33% acetic acid, followed by measuring the absorbance of the extract.

[0061] [Table 5]

[0062] The results for the remaining amount of biofilm are shown in Table 6 below. In Table 6, "Untreated" represents the results for ceramics with a biofilm formed on the surface, and "Blank" represents the results of staining untreated wells with crystal violet.

[0063] [Table 6]

[0064] As shown in Table 6, when the powder composition was added, the relative absorbance was lower in all cases compared to the results for no treatment or sterilized water alone, confirming that the biofilm was decomposed. Note that the blank is an example using a cell culture plate (made of polystyrene) on which no bacteria were seeded, and since no biofilm was formed, the relative absorbance was close to zero.

[0065] The fact that biofilm decomposition was confirmed when a suspension of the powder composition in sterile water was used means that the powder composition itself exhibits antibacterial activity. When the powder composition is used for air abrasion, the physical cutting caused by the spray is added, and it can be fully inferred that in addition to antibacterial activity, the powder composition also exerts the effect of decomposing and removing biofilms.

Claims

1. A powder composition for air abrading the oral cavity, comprising: A powder composition comprising a carrier in which an agent having antibacterial properties is carried on a dental abrasive as a carrier.

2. 2. The powder composition of claim 1, wherein the dental abrasive is a calcium-containing abrasive.

3. 3. The powder composition of claim 1, wherein the dental abrasive is a calcium phosphate compound.

4. 3. The powder composition according to claim 1, wherein the agent having antibacterial properties is a cationic antibacterial agent.

5. 3. The powder composition according to claim 1, wherein the amount of the agent having antibacterial properties carried by the carrier is 0.008 mg / g or more.

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