JPH07206621A - Antimicrobial composition for dentistry - Google Patents

Abstract

PURPOSE:To provide an antimicrobial composition comprising a polymerizable monomer, a polymerization initiator, and a specific amount of a phosphate group-containing polymerizable (meth)acrylate compound, not causing the elution of an antimicrobial ingredient from the composition after polymerization-cured, and capable of being used in a state exposed in an oral cavity. CONSTITUTION:A composition having an antimicrobial property and used for dentistry comprises a polymerizable monomer such as a (meth)acrylic ester or an urethane (meth)acrylic ester, a polymerization initiator such as benzoyl peroxide, and a polymerizable (meth)acrylate compound having a phosphate group of formula I or formula II [e.g. a compound of formula III or a compound of formula IV (n is 4-20)] in an amount of 20-50wt.% based on the sum of the polymerizable monomers in the composition. The composition can be used in a state exposed in an oral cavity as a composite resin for dentistry, an adhesive for dentistry, a resin for denture bases, a coating material for dentistry, an ordinary temperature polymerization type quick polymerization resin, a faveolus fissure-filling material or resin cement for dentistry.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The present invention does not elute antibacterial components,
A non-eluting antibacterial dental composition. Especially used in the state of being exposed in the oral cavity such as dental composite resin, dental adhesive, denture base resin, dental coating material, room temperature polymerization type immediate polymerization resin, pit fissure filling material, dental resin cement etc. Antibacterial dental composition.

[0002]

2. Description of the Related Art Dental caries, which is a typical tooth disease, is caused by dissolution of enamel by an acid produced by microorganisms in the oral cavity. Among them, Streptococcus mutans is
It is listed as an important causative agent of caries. In addition, periodontitis, which is a disease of periodontal tissues, is also believed to occur due to oral bacteria. To prevent any diseases, it is important to prevent the formation of plaque on the tooth surface by these bacteria in the oral cavity or to quickly remove the formed plaque. Is recommended.

On the other hand, when a dental material such as a resin material or a composite resin is used for filling and repairing a carious portion or prosthetic treatment for a defective portion (for example, a denture), plaque is formed on the surface of these materials due to adhesion of bacteria. Since it is easily affected, removal of dental plaque is important for preventing secondary caries and periodontitis.

As a method for preventing caries, a method of improving acid resistance of enamel by applying a so-called fluorine coating to the tooth structure with an acidic fluorophosphoric acid solution, a silver fluoride diamine solution or the like is generally performed. There is. In addition, as a method for preventing the formation of plaque, particularly plaque on the surface of the dental material, some attempts have been made from the standpoint of the material. As one of the attempts, it has been attempted to blend an antibacterial agent into the dental material,
Composite resin containing chlorohexidine (Takemura Kinzo et al., Journal of Japan Dental Conservation Society, Vol. 26, No. 2, 540-540)
Pp. 547, 1983), and calcium phosphate cement mixed with metronidazole (Masaaki Iwahisa et al., Journal of Japan Dental Conservation Society, Vol. 30, No. 5, pp. 1444-1448, 1987).

However, simply blending the antibacterial agent with the dental material as described above causes the antibacterial agent to be eluted from the material in a short period of time, which is not satisfactory in terms of sustainability of the antibacterial effect. In addition, there is a problem that the mechanical properties of the material are deteriorated by blending the antibacterial agent. Furthermore, elution of the antibacterial agent from the dental composition has been concerned not only on the surface of the dental composition but also on the surrounding oral flora.

[0006]

Therefore, the problem to be solved by the present invention is that the antibacterial component does not elute from the dental composition after polymerization and curing, and the antibacterial property is continuously maintained only on the surface of the dental composition. It is an object of the present invention to provide a non-eluting antibacterial dental composition that is expressed and does not cause the growth of oral bacteria around it to be prevented.

[0007]

Means for Solving the Problems The above-mentioned problems are solved by using a polymerizable monomer, a polymerization initiator and a polymerizable (meth) acrylate compound having a phosphoric acid residue shown below as a polymerizable monomer in a composition. This is solved by a dental composition containing 20% by weight or more and 50% by weight or less based on the total weight of the monomers.

Examples of the compound having a phosphoric acid residue of I include the monomers disclosed in JP-B-55-2235. In the above publication, these monomers are comprehensively shown as monomers having the following structures in the molecule, but such types of monomers are also widely used in the present invention.

[Chemical 1]

Examples of the phosphoric acid residue-containing compound of the above II include compounds represented by the following general formula shown in JP-A-58-21607.

[Chemical 2] [However, R ₁ represents H or CH ₃ , and Ra represents a divalent organic group having 4 to 40 carbon atoms. X ₁ and Y ₁ are
It represents O, S or NRb (Rb is H or an alkyl group having 1 to 4 carbon atoms). k represents 0 or 1. ]

In the present invention, the case where R ₁ is H is an acrylate-based polymerizable monomer, and the case where R ₁ is CH ₃ is a methacrylate-based polymerizable monomer. Then, a (meth) acrylate-based polymerizable monomer is used as a notation that means both of them. Hereinafter, unless otherwise specified, the expression of (meth) acrylate is used in the same meaning.

A compound represented by the following structural formula, which has a structure similar to that of the above compound, is also used.

[Chemical 3] [However, m is an integer of 1 to 4. n is an integer of 2 to 6. R '
a is a (m + n) -valent organic group having 5 to 60 carbon atoms. R ₁ , X
₁ , Y ₁ and k are the same as above. ]

Specific examples of the compounds described above are shown below.

[Chemical 4]

[Chemical 5]

The above-mentioned phosphoric acid residue-containing compound must be added to the composition at a compounding ratio of 20% by weight to 50% by weight. If it is less than 20% by weight, the antibacterial effect is insufficient,
If it exceeds 50% by weight, the amount of unpolymerized compound containing a phosphoric acid residue is increased, and uneven spots are formed in the dissolution test. Furthermore, it is not suitable because it causes deterioration of the physical properties of the cured product.

The dental composition of the present invention is a dental composite resin, a dental adhesive, a pit fissure filling material, a denture base resin, a dental coating material, a temporary restoration resin, a dental resin cement. Used as etc. These are formed by appropriately combining, in addition to the above components, an organic polymer, a filler, a stabilizer, a colorant and the like according to the purpose. These important constituent components will be described below.

The polymerizable monomer used in the present invention includes unsaturated carboxylic acids such as α-cyanoacrylic acid, (meth) acrylic acid, crotonic acid, cinnamic acid, sorbic acid, maleic acid and itaconic acid. Esters with mono- 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, N-vinyl Examples thereof include mono-N-vinyl compounds such as pyrrolidone, styrene derivatives, and the like, and the following monofunctional and polyfunctional (meth) acrylic acid esters and urethane (meth) acrylic acid esters are particularly preferable. is there.

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

(Ii) Bifunctional Formula

[Chemical 6] (Wherein 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

[Chemical 7] (Wherein n represents an integer of 1 to 14 and R represents hydrogen or a methyl group). For example, di (meth) acrylates such as ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, dodecaethylene glycol, tetradecaethylene glycol, propylene glycol, dipropylene glycol, and tetradecapropylene glycol, as well as glycerin di (meth) ) 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 2-10 in one molecule, 1,2-bis (3-methacryloxy-
2-hydroxypropoxy) butane and the like.

(Iii) Trifunctional or higher trimethylolpropane tri (meth) acrylate, pentaerythritol tetra (meth) acrylate, etc.

(Iv) Urethane (meth) acrylate-based (meth) acrylate monomer 2 having a hydroxyl group
Reaction product of 1 mol of diisocyanate and N at both ends
Examples thereof include reaction products of a urethane prepolymer of CO and a (meth) acrylate monomer having a hydroxyl group, and the structure of such a reaction product is represented by the following formula.

[Chemical 8] (Here, R ¹ is hydrogen or a methyl group, R ² is an alkylene group, and R ³ is an organic residue.)

As a concrete example, Japanese Examined Patent Publication No. 51-3696
No. 0, the reaction product of 2,2,4-trimethylhexamethylene diisocyanate and oxypropyl methacrylate, the urethane prepolymer of isocyanate at both ends described in JP-B-55-33687, and methacrylic acid- The reaction product with 2-oxyethyl may be mentioned. Further, a tetrafunctional monomer as disclosed in JP-A-56-162408 can also be used.

As the filler (filler) optionally added in the present invention, α-quartz, silica, alumina, hydroxyapatite, calcium carbonate, fluoroaluminosilicate glass, barium sulfate, titanium oxide, zirconia, glass, ultrafine particles It is possible to use an organic composite filler containing silica and an organic component and an inorganic component. In addition, polymethylmethacrylate, a copolymer of methylmethacrylate and a crosslinkable monomer, polymer powder of polystyrene, polyvinyl chloride or the like is added as necessary. Such glass, 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, Examples thereof include synthetic silica and titanium silicate glass.

The inorganic filler used in the present invention includes:
It is desirable to use it after surface treatment. As the surface treatment agent, an organic silicon compound such as γ-methacryloxypropyltrimethoxysilane, vinyltrichlorosilane, vinyltriethoxysilane, vinyltrimethoxysilane, vinyltriacetoxysilane and vinyltri (methoxyethoxy) silane is used. The conversion is carried out by a usual method.

Examples of the polymerization initiator used in the present invention include peroxides such as benzoyl peroxide and cumene hydroperoxide, tributyl borane, benzoyl peroxide-aromatic tertiary amines, aromatic sulfinic acid (or its Salt) -aromatic secondary or tertiary
A room temperature polymerization initiator such as a primary amine-acyl peroxide type may be used. Furthermore, camphorquinone, camphorquinone-tertiary amine system, camphorquinone-peroxide,
Camphorquinone-aldehyde type, camphorquinone-
Examples include photopolymerization initiators such as mercaptan-based and acylphosphine oxides. When photopolymerization is carried out by ultraviolet irradiation, benzoin methyl ether, benzyl dimethyl ketal, benzophenone, 2-
Methylthioxanthone, diacetyl, benzyl, azobisisobutyronitrile, tetramethylthiuram disulfide and the like are preferable.

Further, the composition of the present invention may optionally contain
A polymerization inhibitor, a colorant, a fluorescent agent, an ultraviolet absorber, etc. can be added.

[0026]

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

(Method for preparing test piece) A composition having a diameter of 20
It was filled in a metal mold having a thickness of 0.5 mm and a thickness of 0.5 mm, and both surfaces were irradiated with light for 1 minute to polymerize and cure to prepare a disc-shaped test piece.
The obtained test piece was washed with acetone and methanol to remove unpolymerized monomer on the surface, and then sterilized with ethylene oxide gas.

(Antibacterial Test Method) mutans (I
FO13955) was cultured overnight in BHI (Brain Heart Infusion) medium, and the bacterial concentration was 5 × 10 5.
^It was diluted with physiological saline to ³ (CFU / ml). 10 μl of this diluted solution was dropped onto a test piece using a micropipettor, left standing for 15 minutes, the test piece was turned upside down, and the solution on the test piece was pressed against a BHI agar medium to recover residual bacteria. . Furthermore, the test piece is B
All the bacteria were collected on the agar medium by pressing on 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. Based on the number of formed colonies and the total number of inoculated bacteria, the bacterial mortality of each sample was calculated according to the following calculation formula.

[Equation 1]

Similarly, the bacterial concentration was 5 × 10 5.
^The exact same test was performed using a bacterial diluent diluted to ⁴ (CFU / ml) and 5 × 10 ⁵ (CFU / ml). In addition, S. The same test as above was carried out using B. subtilis (IFO13721), Staphylococcus (S. aureus, IFO12732), Escherichia coli (E. coli., IFO12734) instead of mutans.

When the above-mentioned bacterial killing rate is 100%,
It shows that all the bacteria inoculated on the sample were killed, and that the surface of the sample exhibited extremely strong antibacterial property. On the contrary, when the bacterial death rate is 0%, it means that all the inoculated bacteria are alive and that the sample surface has no antibacterial property. Furthermore, if the bacterial killing rate is between 0% and 100%,
Although it cannot completely kill bacteria, it shows that it has some antibacterial properties. For the purpose of the present invention, a mortality rate of 100% is preferable, but when the mortality rate is 80% or more, it is judged that the purpose can be sufficiently achieved.

(Dissolution test method) mutans (IF
O13955) was cultured overnight in BHI (Brain Heart Infusion) medium, and the bacterial concentration was 1 × 10 ^6.
It was diluted with physiological saline so as to be (CFU / ml).
This diluted solution was applied to a BHI agar plate and then dried. The test piece was placed thereon, and after aerobically culturing at 37 ° C. for 48 hours, the presence or absence of inhibition spots formed around the test piece was observed and evaluated according to the following criteria. (+): An inhibition spot in which the growth of bacteria was suppressed was formed around the sample. (-): No inhibition spots were formed around the sample.

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

As a result of the above judgment, (+) indicates that the antibacterial substance was eluted from the surface of the sample, and there is a demand for the expression of non-eluting antibacterial property which is one of the objects of the present invention. It means that it does not meet. Even if the sample showed 100% mortality as a result of the above-mentioned antibacterial property test, it is judged that the object of the present invention cannot be achieved if the inhibition spots are formed in this dissolution test.

Example 1 As shown in Table 1, 26.5 parts by weight of BisGMA, 3
G (triethylene glycol dimethacrylate) 26.
5 parts by weight, MDP (metalloyloxydecyl dihydrogen phosphate) 50 parts by weight, camphorquinone 1 part by weight, dimethylaminoethyl methacrylate 2
A monomer mixture consisting of parts by weight was prepared. Quartz powder surface-treated with 50 parts by weight of this monomer mixture and γ-methacryloxypropyltrimethoxysilane (average particle size 2.4
μm) 50 parts by weight were mixed to prepare a paste-like composition. Using the composition, a test piece was prepared by the above-mentioned method, and the antibacterial property against 4 kinds of bacteria was evaluated according to the above-mentioned antibacterial property test method. The results are shown in Table 2. Further, using a test piece prepared by the same method, it was examined according to the above-mentioned dissolution test method whether or not inhibition plaques were formed for four kinds of bacteria.
The results are shown in Table 3.

Examples 2 to 4 As shown in Table 1, in the composition of Example 1, the compounding ratio of MDP was 40 parts by weight (Example 2), 30 parts by weight (Example 3), 20 parts by weight. Part (Example 4), BisGMA,
Three kinds of monomer mixtures having a high 3G compounding ratio were prepared and mixed in an equal amount with quartz powder in the same manner as in Example 1 to prepare a paste composition. Using the composition, test pieces were prepared in the same manner as in Example 1 and evaluated for antibacterial activity against 4 kinds of bacteria. The results are shown in Table 2. Further, using a test piece prepared by the same method, as in Example 1, the presence or absence of inhibition plaque formation for 4 types of bacteria was examined. The results are shown in Table 3.

Comparative Example 1 As shown in Table 1, a monomer mixture was prepared by increasing the compounding ratio of MDP to 60 parts by weight in the composition of Example 1 and decreasing the compounding ratio of BisGMA and 3G. In the same manner as in Example 1, an equal amount of quartz powder was mixed to prepare a paste-like composition. Using the composition, test pieces were prepared in the same manner as in Example 1 and evaluated for antibacterial activity against 4 kinds of bacteria. The results are shown in Table 2. Further, using a test piece prepared by the same method, as in Example 1, the presence or absence of inhibition plaque formation for 4 types of bacteria was examined. The results are shown in Table 3.

Examples 2 to 4 As shown in Table 1, in the composition of Example 1, the compounding ratio of MDP was 10 parts by weight (Comparative Example 2), 5 parts by weight (Comparative Example 3), and 0 parts by weight. Part (Comparative Example 4), BisGMA, 3
Prepare 3 kinds of monomer mixture with high G compounding ratio,
In the same manner as in Example 1, an equal amount of quartz powder was mixed to prepare a paste composition. Using the composition, test pieces were prepared in the same manner as in Example 1 and evaluated for antibacterial activity against 4 kinds of bacteria. The results are shown in Table 2. Further, using a test piece prepared by the same method, as in Example 1, the presence or absence of inhibition plaque formation for 4 types of bacteria was examined. The results are shown in Table 3.

[0038]

[Table 1]

[0039]

[Table 2]

[0040]

[Table 3]

[0041]

The composition of the present invention is covalently fixed in the composition after polymerization because the antibacterial component itself has polymerizability. Therefore, the antibacterial component does not elute in water (saliva), and the antibacterial property is semipermanently retained even when used in the oral cavity. Furthermore, since this antibacterial property is limited to the surface of the composition, it does not destroy the bacterial flora in the oral cavity. Therefore, when the present composition is used as a dental material, it has an effect of preventing adhesion of bacterial plaque causing caries or periodontal disease for a long period of time while minimizing side effects.

Claims (1)

[Claims] 1. A polymerizable monomer, a polymerization initiator, and a polymerizable (meth) acrylate compound having a phosphoric acid residue shown below in an amount of 20 relative to the total weight of the polymerizable monomers in the composition. A dental composition having antibacterial properties, characterized in that it is contained in an amount of not less than 50% by weight.