JPH1025218A - Antimicrobial filler - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare an antimicrobial filler, suitable for blending in a molding material, a dental filler, etc., and having noneluting type antimicrobial activities without eluting an antimicrobial ingredient by coating the surface of an inorganic filler with a specific polymer having antimicrobial activities. SOLUTION: This antimicrobial filler is prepared by coating the surface of an inorganic filler with a polymer prepared by polymerizing polymerizable monomers containing at least one antimicrobial polymerizable monomer selected from compounds represented by formula I [R1 is H or CH3 ; R2 is an alkylene; X is O, S, etc.; (m) and (n) are each 0 or 1; (p) is 1-3; Y is ≡N<+> Z<-> -R3 R3 is (X)q -R6 -W [R6 is an alkylen; W is H, CH3 , etc.; (q) is 0 or 1]; Z is Cl, Br, etc.}], formula II [R4 is (X)q -R5 -W (R5 is an alkylene)], formula III (R3 , R4 , R6 and R7 are each H or an alkyl; R5 is an alkylene; R8 is an alkyl, etc.; Z and Y are each Cl, Br, etc.), are formula IV (R<1> is H or CH3 ; X is O or NH; R<2> is CO, O, S, etc.; R<4> and R<5> are each H, an alkyl, etc.; R<3> is an alkyl; Z is a halogen). A composite resin using the filler is capable of preventing a plaque from forming.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a non-eluting antibacterial filler which does not elute an antibacterial component. More specifically, the present invention relates to an antibacterial filler suitable for blending into various resin products, particularly molding materials, dental fillers and the like.

[0002]

2. Description of the Related Art In recent years, many attempts have been made to blend various antibacterial agents with the aim of imparting antibacterial properties to the surface of resins, molding materials, etc., but the antibacterial properties are due to elution of the antibacterial agents. However, there is a problem that the antibacterial property is lost after all the antibacterial agents are eluted. Many attempts have been made to mix antibacterial metal ions in place of antibacterial agents, but these are also thought to be due to the effect of elution of antibacterial metal ions. It had the problem of being lost. Furthermore, in order to control the dissolution rate of antibacterial metal ions, it has been studied to mix a carrier such as zeolite, hydroxyapatite, and glass with antibacterial metal ions, but the effect of extending the dissolution period has been studied. However, a permanent effect could not be expected because all of the antibacterial metal ions were eluted sooner or later.

[0003] In the field of dental materials, plaque based on the adhesion of bacteria is easily formed on the surface of a composite resin or the like. Therefore, these materials are used to repair the filling of carious parts and to repair defective parts (for example, dentures). ) Is problematic because it tends to cause secondary caries and periodontitis. Therefore, Japanese Patent Application Laid-Open No. 1-238508 discloses a dental material containing glass filler, zeolite, hydroxyapatite or the like containing antibacterial silver ions. It had antibacterial properties, and had problems such as persistence of antibacterial properties and destruction of the bacterial flora in the oral cavity.

[0004] In order to solve these problems, the present applicant disclosed in the invention of Japanese Patent Application No. 4-274577 an antibacterial dental composition containing an antibacterial polymerizable monomer.
It was shown that a non-eluting antibacterial property was developed on the surface of the composition after polymerization and curing.

However, the antibacterial property of the surface of the above-mentioned antibacterial dental composition after polymerization and curing is limited to the matrix polymer portion. Fillers are often added to dental compositions for the purpose of improving their mechanical strength.When the cured product after molding is polished, the matrix polymer portion having antibacterial properties on the surface is removed, and the antibacterial properties are removed. Unfilled fillers are exposed. In the case of a composite resin or the like, since the compounding ratio of the filler is very high, the area of the polished surface where the filler is exposed is larger than that of the matrix polymer. Accordingly, there is a problem that the antibacterial property of the surface of the composite resin after polishing is significantly reduced as compared with that before polishing, and the effect of preventing bacterial adhesion is reduced.

[0006] As fillers to be blended in dental composite resins, inorganic fillers are often used, but Japanese Patent Application Laid-Open Nos. 56-20066 and 59-10
No. 1409, JP-A-60-71621, JP-A-60-119270, JP-A-62-1927.
No. 0 discloses a technique of an organic composite filler in which an inorganic filler is coated with an organic substance for the purpose of improving the abrasiveness of a composite resin, improving mechanical strength, and the like. However, there is no description about a method for imparting antibacterial properties to these organic composite fillers.

[0007]

The problem to be solved by the present invention is to solve the above-mentioned problems and to provide a resin product, particularly a molding material and a dental material, having more excellent antibacterial properties on the surface. .

[0008]

The present inventors have intensively studied means for solving the above-mentioned problems, and as a result, imparted an antibacterial property to a filler component occupying a large area in a polished surface of a resin product, It has been found that the above problem can be achieved by increasing the ratio of the surface area having antibacterial properties. That is, in the present invention, the surface of the inorganic filler is polymerized with a polymerizable monomer containing at least one antibacterial polymerizable monomer selected from the compounds represented by the following general formulas (1) to (4). An antimicrobial filler characterized by being coated with coalescence.

[0009]

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[0010]

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[0011]

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[0012]

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The antibacterial filler of the present invention is produced by adding a polymerization initiator to a mixture of an antibacterial polymerizable monomer and an inorganic filler and pulverizing a cured product polymerized by heating or light irradiation. be able to. Alternatively, it can be produced in the form of a powdery filler by adding a polymerization initiator to an antibacterial polymerizable monomer and an inorganic filler and polymerizing the mixture in a suspended state. Furthermore, a powdery filler can be produced by polymerizing a mixture of an antibacterial polymerizable monomer and an inorganic filler to which a polymerization initiator has been added and spraying and dispersing the mixture.

The antibacterial filler of the present invention may be produced by blending a polymerizable monomer having no antibacterial property in addition to the polymerizable monomer having the antibacterial property as required. .
In this case, it is desirable to add a polyfunctional polymerizable monomer having two or more polymerizable groups in one molecule for the purpose of increasing the strength of the antibacterial filler after polymerization.

In order for the antibacterial filler of the present invention to have sufficient antibacterial properties, the amount of the polymerizable monomer having antibacterial properties should be such that the content of the polymerizable monomers having antibacterial properties is: 1% by weight or more and 80% by weight or less based on the total weight of the polymerizable monomers in the composition, more preferably 5% by weight
Not less than 60% by weight.

The content of the polymerizable monomer having antibacterial properties is
If the amount is less than 1% by weight based on the total amount of the polymerizable monomers in the composition, the desired antibacterial property cannot be obtained.

For the purpose of expressing only the antibacterial property, the effect is greater as the content of the polymerizable monomer having the antibacterial property increases. However, when the content of these compounds is increased, the strength of the obtained filler is reduced, and the mechanical strength when the dental composition containing them is cured is reduced, so that a polymerizable polymer having antibacterial properties is obtained. The content of the monomer is 80% by weight based on the total amount of the polymerizable monomers in the composition.
It is necessary to keep it below.

[0018] The antibacterial filler of the present invention comprises 50 to 85% by weight of inorganic filler (more preferably 60 to 70% by weight).
And polymerized at a rate of 50 to 15% by weight of a polymerizable monomer. The higher the blending ratio of the polymerizable monomer, the higher the ratio of the antibacterial polymerizable monomer exposed on the filler surface after pulverization, so that a filler having a high antibacterial property can be obtained. Since the amount decreases, a problem arises that the thermal expansion coefficient increases. Taking these performances into consideration, a desirable compounding ratio is determined.

The antibacterial filler of the present invention is used by being added to a raw material monomer such as a resin or a molding material. In particular, it is preferable to use it by blending it with a dental composite resin, a dental adhesive, a pit and fissure filling material, a denture base resin, a dental coating material, a temporary restoration resin, a dental resin cement, and the like. is there. When compounding a filler into a dental composite resin, the surface of the filler is treated with a silane coupling agent to strengthen the bond between the filler and the matrix polymer portion. Also, because there is a part where the inorganic filler is exposed,
Preferably, a silane treatment is performed. Various silane treatment agents can be used, and γ-methacryloxypropyltriethoxysilane is preferred.

The antibacterial polymerizable monomer used in the present invention includes compounds represented by the following general formulas (1) to (4).

[0021]

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[0022]

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[0023]

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[0024]

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Specific examples of the compound represented by the general formula (1) include compounds having the following structural formulas.

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Specific examples of the compound represented by the general formula (2) include a compound represented by the following structural formula.

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Specific examples of the compound represented by the general formula (3) include compounds having the following structural formulas.

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Specific examples of the compound represented by the general formula (4) include compounds having the following structural formulas.

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The polymerizable monomer used as required in the present invention includes unsaturated monomers such as (meth) acrylic acid, α-cyanoacrylic acid, crotonic acid, cinnamic acid, sorbic acid, maleic acid and itaconic acid. Esters of carboxylic acids with monohydric or dihydric alcohols, (meth) acrylamides such as N-isobutylacrylamide, vinyl esters of carboxylic acids such as vinyl acetate,
Vinyl ethers such as butyl vinyl ether;
Mono-N-vinyl compounds such as vinylpyrrolidone, styrene derivatives and the like are mentioned. In particular, the following (meth) acrylic esters and urethane (meth)
Acrylic esters are preferred.

(I) Monofunctional methyl (meth) acrylate, n- or i-propyl (meth) acrylate, n-, i- or t-butyl (meth) acrylate, 2-hydroxyethyl (meth) Acrylate and the like.

(Ii) Bifunctionality The general formula is

Embedded image (Where n represents an integer of 3 to 20, and R represents hydrogen or a methyl group). For example, di (meth) acrylates such as propanediol, butanediol, hexanediol, octanediol, nonanediol, decanediol, and eicosanediol.

The general formula is

Embedded image (Where n is an integer of 1 to 14, R represents hydrogen or a methyl group). For example, in addition to di (meth) acrylates such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, dodecaethylene glycol, tetradecaethylene glycol, propylene glycol, dipropylene glycol, and tetradecapropylene glycol, glycerin di (meth) acrylate ) Acrylate, 2,2-bis [4-
(3-methacryloyloxy-2-hydroxypropoxy) phenyl] propane (Bis-GMA), bisphenol A dimethacrylate, neopentyl glycol di (meth) acrylate, 2,2-di (4-methacryloxypolyethoxyphenyl) propane ( Ethoxy groups 2 to 10), 1,2-bis (3-methacryloxy-
2-hydroxypropoxy) butane and the like.

(Iii) Trifunctional or higher trimethylolpropane tri (meth) acrylate, pentaerythritol tetra (meth) acrylate and the like.

(Iv) Urethane (meth) acrylate monomer (meth) acrylate monomer 2 having a hydroxyl group
Reaction product of 1 mole of diisocyanate and 1 mole of diisocyanate
Examples of the reaction product include a reaction product of a urethane prepolymer of CO and a (meth) acrylate monomer having a hydroxyl group. The structure of the reaction product is represented by the following formula.

Embedded image (Where R ₁ is hydrogen or a methyl group, R ₂ is an alkylene group, and R ₃ is an organic residue.)

As a specific example, Japanese Patent Publication No. 51-3696
No. 0, a reaction product of 2,2,4-trimethylhexamethylene diisocyanate with oxypropyl methacrylate, and a urethane prepolymer of both terminal isocyanates described in JP-B-55-33687 and methacrylic acid- Reaction products with 2-oxyethyl are mentioned. Further, a tetrafunctional monomer as disclosed in JP-A-56-162408 may be used.

The inorganic filler used in the present invention includes α-quartz, silica gel, synthetic spherical silica, ultrafine silica, alumina, hydroxyapatite, calcium carbonate, fluoroaluminosilicate glass, barium sulfate, titanium oxide, zirconia, and various types of glass. Etc. can be used. Examples of such glass include silica glass, soda-lime silicate glass, borosilicate glass, barium glass, strontium glass, zinc glass, lanthanum glass, yttria glass, barium boroaluminosilicate glass, alumina silicate glass, strontium boroaluminosilicate glass, Titanium silicate glass and the like can be mentioned.

The above-mentioned inorganic filler is preferably subjected to a surface treatment with a silane coupling material in advance in order to strengthen the bond with the polymerizable monomer. It is possible. As the silane treatment material, γ-methacryloxypropyltriethoxysilane is preferable.

The radical polymerization initiator used in the present invention includes peroxide-based thermal polymerization initiators such as benzoyl peroxide and cumene hydroperoxide;
Tributylborane, benzoyl peroxide-aromatic tertiary amine, aromatic sulfinic acid (or salt thereof)
-Room temperature polymerization initiators such as aromatic secondary or tertiary amine-acyl peroxides. Furthermore, if necessary, photopolymerization initiators such as camphorquinone, camphorquinone-tertiary amine-based, camphorquinone-peroxide, camphorquinone-aldehyde-based, camphorquinone-mercaptan-based, and acylphosphine oxide are exemplified. be able to. When photopolymerization by ultraviolet irradiation is performed, benzoin methyl ether, benzyl dimethyl ketal, benzophenone, 2-methylthioxanthone, diacetyl, benzyl, azobisisobutyronitrile, tetramethylthiuram disulfide, and the like are preferable.

[0039]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

(Method of Preparing Test Specimen)
The mold was placed in a mold having a thickness of 0.5 mm and a thickness of 0.5 mm, and both sides were irradiated with light for 1 minute to be polymerized and cured to prepare a disk-shaped test piece.
The surface of the obtained test piece was coated with silicon carbide abrasive paper (#
After polishing in 1000), the polymer was washed with acetone and methanol to remove unpolymerized monomers on the surface, and sterilized with ethylene oxide gas.

(Antibacterial test method) mutans (I
FO13955) was cultured overnight in a BHI (Brain Heart Infusion) medium and the bacterial concentration was 5 × 10 5
^The solution was diluted with physiological saline to ³ (CFU / ml). 10 μl of this diluted solution was dropped on the test piece using a micropipettor, and allowed to stand as it was for 15 minutes. Then, the test piece was turned upside down, and the solution on the test piece was pressed against a BHI agar medium to collect residual bacteria. . Further, the test piece is
All the bacteria were collected on the agar medium by pressing against different parts of the HI agar medium. Then, after performing aerobic culture at 37 ° C. for 48 hours, the number of colonies formed on the agar medium was counted. For each sample, based on the number of formed colonies and the total number of inoculated bacteria, the bacterial kill rate was determined according to the following formula.

(Equation 1)

Similarly, when the bacterial concentration is 5 × 10
Exactly the same test was performed using a bacterial dilution diluted to ⁴ (CFU / ml), 5 × 10 ⁵ (CFU / ml). Further, S.I. The same test as described above was performed using B. subtilis (IFO13721), staphylococci (S. aureus, IFO12732), and Escherichia coli (E. coli, IFO12734) instead of B. mutans.

When the above-mentioned bacterial kill rate is 100%,
This indicates that all the bacteria inoculated on the sample have been killed, indicating that a very strong antibacterial property has been expressed on the sample surface. Conversely, a bacterial kill rate of 0% indicates that all the inoculated bacteria are alive and that the sample surface has no antimicrobial activity. Furthermore, if the bacterial kill rate is between 0% and 100%,
Although it cannot kill bacteria completely, it shows that it has some antibacterial properties.

(Dissolution test method) mutans (IF
O13955) was cultured overnight in a BHI (Brain Heart Infusion) medium, and the bacterial concentration was 1 × 10 ^6.
(CFU / ml) with physiological saline.
This diluted solution was applied to a BHI agar plate and dried. After placing the test piece thereon and performing aerobic culture at 37 ° C. for 48 hours, the presence or absence of inhibition spots formed around the test piece was observed, and the evaluation was made according to the following criteria. (+): Inhibition spots were formed around the sample where bacterial growth was suppressed. (-): No inhibition patch was formed around the sample.

Further, S.I. Instead of B. mutans, Bacillus subtilis (B. subtilis, IFO13721), staphylococcus (S. aureus, IFO12732), E. coli (E. coli., IFO12734) were used.
The exact same test was performed as above.

As a result of the above judgment, a (+) indicates that the antibacterial substance was eluted from the sample surface, and the requirement of the expression of non-elutable antibacterial property, which is one of the objects of the present invention, was met. Will not be satisfied. As a result of the antibacterial test described above, even if the sample showed a kill rate of 100%, the sample in which the inhibition spot was formed in this dissolution test was judged to be unable to achieve the object of the present invention.

(Measurement of bending strength)
m, a thickness of 2 mm, and a depth of 2 mm were charged into a mold, and both sides were irradiated with light for 1 minute to be polymerized and cured to prepare a columnar test piece. The bending strength of the obtained test piece was measured using an Instron universal testing machine.

Examples 1 to 7 Antibacterial monomers A (methacryloyloxidedecylpyridinium bromide, hereinafter abbreviated as MDPB), N,
N ′-(1,2,4-trimethylhexamethylene) bis (2-aminocarboxy) propane-1,2-diol) tetramethacrylate (hereinafter abbreviated as U-4TH), triethylene glycol dimethacrylate (hereinafter 3G) Abbreviated) and benzoyl peroxide (hereinafter abbreviated as BPO) in the proportions shown in Table 1 and then dissolved in solution 6
Light silicic acid (Aerosil OX-5)
0) After adding 40 g and kneading in a mortar, the mixture was defoamed under reduced pressure to obtain a paste-like composition. This composition is 3 m thick
m, and heated under vacuum at 120 ° C. for 5 hours,
After obtaining the polymerized cured product, it was pulverized in a mortar and collected through a 150-mesh sieve. 5 g of γ-methacryloxypropyltrimethoxysilane (hereinafter abbreviated as γ-MPS) is added to 150 ml of 0.1% acetic acid aqueous solution, stirred at room temperature for 15 minutes, 100 g of the above pulverized material is added, and reacted at room temperature for 2 hours. After that, freeze-drying was performed. In addition, 9
After performing heat treatment at 0 ° C. for 3 hours, vacuum drying was performed at 40 ° C. for 16 hours to obtain a filler.

5 g of this filler, 3 g of quartz powder surface-treated with γ-MPS, 10 g of 3G, 2,2-bis [4- (3
-Methacryloyloxy-2-hydroxypropoxy)
Phenyl] propane (hereinafter abbreviated as Bis-GMA)
10 g, camphorquinone (hereinafter abbreviated as CQ) 1
g, dimethylaminoethyl methacrylate (hereinafter DMA)
After mixing 2 g (abbreviated as EMA), the mixture was kneaded in a mortar to prepare a composite resin paste. Using this composite resin paste, test pieces were prepared by the above-described method, and antibacterial properties against four kinds of bacteria were evaluated according to the above-mentioned surface antibacterial test method. Table 1 shows the results. In addition, using test pieces prepared in the same manner, the presence or absence of formation of inhibitory spots on four kinds of bacteria was observed according to the above-described dissolution test method. Table 1 shows the results. Further, the bending strength was measured according to the above-described bending strength test method.

Examples 8 to 14 MDPB, U-4TH, CQ and DMAEMA were dissolved in the proportions shown in Table 2. 40 g of light anhydrous silicic acid (Aerosil OX-50) was added to 60 g of this solution, kneaded in a mortar, and then defoamed under reduced pressure to obtain a paste-like composition. This composition was spread into a plate having a thickness of 3 mm, irradiated with light from each side for 5 minutes using a slide projector (HILUX-H130, manufactured by Rikagaku Seiki Co., Ltd.) to obtain a polymerized cured product, and then ground in a mortar. , Were passed through a 150 mesh sieve. 5 g of γ-methacryloxypropyltrimethoxysilane (hereinafter abbreviated as γ-MPS) is added to 150 ml of 0.1% acetic acid aqueous solution, stirred at room temperature for 15 minutes, 100 g of the above pulverized material is added, and the mixture is reacted at room temperature for 2 hours. After that, freeze-drying was performed. Furthermore, after performing a heat treatment at 90 ° C. for 3 hours, vacuum drying was performed at 40 ° C. for 16 hours to obtain a filler. Further, a composite resin paste containing the filler was prepared and polymerized and cured by the same operation as in Example 1, and then a surface antibacterial test, an inhibitory spot formation test, and a measurement of bending strength were performed. Table 2 shows the results.

Examples 15 to 24 Instead of the antibacterial polymerizable monomer MDPB of Example 5, antibacterial monomers B to K were used to prepare U-4TH, 3G, BP
O was dissolved in the proportions shown in Table 3. Hereinafter, the fillers of Examples 15 to 24 were obtained by the same operation as in Example 5.
Furthermore, a composite resin paste containing the filler was prepared and polymerized and cured by the same operation as in Example 5, and then a surface antibacterial test, an inhibitory spot formation test, and a measurement of bending strength were performed. Table 3 shows the results.

Comparative Examples 1 to 3 MDPB, 3G, U-4TH and BPO were dissolved at the ratios shown in Table 1. Thereafter, OX is performed by the same operation as in Example 1.
After mixing with -50, polymerization and pulverization were performed to obtain a filler.
Further, a composite resin paste containing the filler was prepared and polymerized and cured by the same operation as in Example 1, and then a surface antibacterial test and an inhibitory spot formation test were performed. Table 1 shows the results.

Comparative Examples 4 to 6 MDPB, 3G, U-4TH, CQ and DMAEMA were dissolved in the proportions shown in Table 2. Thereafter, by the same operation as in Example 8, after mixing with OX-50, polymerization and pulverization were performed to obtain a filler. Further, a composite resin paste containing the filler was prepared and polymerized and cured by the same operation as in Example 1, and then a surface antibacterial test and an inhibitory spot formation test were performed. Table 2 shows the results.

As is clear from Tables 1 to 3, Examples 1 to
In the case of the composite resin using 24 fillers, a strong antibacterial property capable of killing all four types of bacteria adhered to the polished surface after polymerization and curing was confirmed. Furthermore, since no inhibition spots were formed around the composite resin after the polymerization and curing, it was confirmed that no antibacterial component was eluted from the surface of the composite resin. In contrast, when the fillers of Comparative Examples 1 and 4 were used,
Although strong antibacterial properties were confirmed on the polished surface after the polymerization and curing, it was confirmed that the bending strength of the composite resin was very weak. In addition, when the fillers of Comparative Examples 2 and 3 were used, although the bending strength of the composite resin was high,
Bacteria attached to the surface of the composite resin could not be killed.

[0055]

According to the present invention, a non-eluting antibacterial filler having antibacterial properties is provided. By blending the antibacterial filler of the present invention as a filler for a dental composite resin, it becomes possible to express strong antibacterial properties on the polished surface after polymerization and curing, and to form bacterial plaque on the filled composite resin surface. It became possible to prevent it semi-permanently. In addition, it is possible to impart a strong antibacterial property to the surface by blending it with dental materials used by blending fillers such as hard resins for crowns other than composite resins, dentures, denture base materials, resin cement, etc. became.

[0056]

[Table 1]

[0057]

[Table 2]

[0058]

[Table 3]

Claims (1)

[Claims] 1. A polymer in which the surface of an inorganic filler is polymerized with a polymerizable monomer containing at least one antibacterial polymerizable monomer selected from compounds represented by the following general formulas (1) to (4): An antibacterial filler characterized by being coated with. Embedded image Embedded image Embedded image Embedded image