JPH10259109A - Antimicrobial dental composition and antimicrobial dental polymer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antibacterial dental composition and an antibacterial dental which are non-eluting type dental polymers useful for dental range materials and which can exhibit antibacterial properties only on the surface of the dental polymer. Provide a polymer for use. SOLUTION: As an antibacterial agent, the following general formula (1); (Wherein R ¹ , R ² and R ³ are the same or different and are each a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, an aryl group, an aralkyl group, a hydroxy group or an alkoxy group. Represents an alkyl group, an aryl group or an aralkyl group substituted by X, X ⁻ represents an anion, and n represents an integer of 1 or more.) A dental composition and an antibacterial dental polymer obtained by polymerizing the same.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a vinylbenzylphosphonium which is a non-elutable polymer useful for an antibacterial dental composition and a dental range material and which can exhibit antibacterial properties only on the surface of the dental polymer. The present invention relates to an antibacterial dental polymer containing a salt monomer as an active ingredient.

[0002]

2. Description of the Related Art At present, as a method for cleaning dental materials after treatment, for example, in the case of a molded restoration material, soiling of floor materials is performed by a commercially available cleaning agent or a mechanical method by scaling. I have. However, in any case, there are restrictions on the place and time. In particular, when the floor material is very dirty, such as plaque, it takes time to clean and it is difficult to completely remove the soil.

At present, it is impossible to consider the hygiene aspects of dental materials after treatment except for the scaling method, except for the patient's own hygiene concept, such as postoperative secondary caries and denture stomatitis. It is an important problem to control such factors. Maintaining a long and clean oral environment is important not only to prevent primary and secondary diseases, but also to be physically healthy and to lead a mentally comfortable and healthy daily life. .

It is said that the secondary caries is caused by microorganisms in the oral cavity. Above all, mutans bacteria (Streptococcus Mutans) are known as important causative bacteria of caries. Plaque formation is considered to be greatly involved in other diseases. As a method for preventing caries, a method of improving the acid resistance of enamel by applying an acidic fluorophosphoric acid solution, a silver diamine fluoride solution, or the like, that is, applying fluorine, is generally performed. Some attempts have been made to prevent the formation of plaque, particularly plaque on the surface of dental materials, from the viewpoint of materials. As one of the attempts, a method of blending an antibacterial agent with a dental material has been proposed. For example, dental materials containing chlorohexidine (Kingo Takemura et al., Journal of the Japanese Society of Dental Conservation, Vol. 26, No. 2, pp. 540-547, 1983),
Calcium phosphate cement containing metronidazole (Iwahisa Masaaki et al., Journal of the Japanese Society of Dental Conservation, Vol. 30, No. 5, 1)
444-1448 (1987), a dental material composition containing a metal-containing inorganic compound antibacterial agent containing metal ions such as silver, copper and zinc (Japanese Patent Application Laid-Open No. 01-2385).
No. 08), a dental resin composition containing an antibacterial zeolite (Japanese Patent Application Laid-Open No. 02-142711), and a dental cement composition containing a calcium-supported compound carrying silver as an antibacterial component (Japanese Patent Application Laid-Open No. -16522
No.) has been proposed.

[0005] However, the above-mentioned ones are obtained by simply blending an antibacterial agent into a dental material, and the antibacterial component elutes in a short time or the bonding between the antibacterial agent and the dental material is insufficient. Not only is it easy for the antimicrobial agent itself to be released from the dental material easily, but the elution of the antimicrobial component from the dental material is not only a matter of the shape of the surface of the dental material, but also to the oral bacteria around it. There is a concern about the impact. Therefore, the non-eluting antibacterial polymer is a non-eluting antibacterial polymer that exhibits sustained antibacterial activity only on the surface of the dental composition and does not inhibit the growth of oral bacteria around the dental composition. Things have been suggested. To solve these problems, for example, an antibacterial dental material composition obtained by polymerizing an ethylenically unsaturated monomer and a specific monofunctional or trifunctional antibacterial monomer (Japanese Patent Application Laid-Open No. 06-9725); Dental compositions containing a polymerizable monomer, a polymerization initiator, and a polymerizable (meth) acrylate compound having a specific amount of a phosphoric acid residue (JP-A-07-206621 and JP-A-07-215814) ) Etc. have been proposed.

However, bacteria that promote the formation of plaque are S. Mutans, S. Sanguis, S. Mitor, S. Milleri, S.
Salivarius and others are known, and furthermore, the adhesion mechanism of bacteria to dental materials varies greatly depending on the bacterial species, so that conventional non-eluting antibacterial polymers cannot expect antibacterial effects against all bacteria Not only that, it has a drawback that it has low antibacterial activity against S. Mutans, which is a causative bacterium.

[0007]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a non-eluting type dental polymer useful for a dental range material and an antibacterial property capable of exhibiting antibacterial properties only on the surface of the dental polymer. It is to provide a dental composition and an antibacterial dental polymer.

[0008]

Means for Solving the Problems In view of the above problems, the present inventors have conducted intensive studies on a non-eluting antibacterial polymer useful as an antibacterial dental material. The present inventors have found that a dental polymer containing a body as an active ingredient continuously exhibits antibacterial activity only on the surface of the polymer, and have completed the present invention.
That is, the present invention provides the following general formula (1) as an antibacterial agent:

[0009]

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(Wherein R ¹ , R ² and R ³ are the same or different and are each a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, an aryl group, an aralkyl group,
It represents an alkyl group, an aryl group or an aralkyl group substituted with a hydroxy group or an alkoxy group, X ^- represents an anion, and n represents an integer of 1 or more. The present invention provides an antibacterial dental composition containing a vinylbenzylphosphonium salt-based monomer represented by the formula (1) as an active ingredient and an antibacterial dental polymer obtained by polymerizing the same.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The antibacterial dental composition of the present invention comprises:
The vinylbenzylphosphonium salt-based monomer represented by the general formula (1) is used as an active ingredient. In the general formula (1), examples of the linear or branched alkyl group having 1 to 18 carbon atoms include groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, and dodecyl. And the aryl group is phenyl,
Groups such as tolyl and xylyl are exemplified, and aralkyl groups include groups such as benzyl and phenethyl. Examples of the alkyl group, aryl group and aralkyl group in the alkyl group, aryl group and aralkyl group substituted with a hydroxy group or an alkoxy group include the same as the above-mentioned alkyl group, aryl group and aralkyl group. Among the above, preferred alkyl groups include butyl, heptyl and octyl groups, and preferred aryl groups include phenyl and tolyl groups. Particularly preferred R ^{1 to} R ³ are alkyl groups such as butyl group, heptyl group and octyl group, and R ^{1 to} R ³ may be the same or different groups. .

In the general formula (1), n represents an integer of 1 or more. Examples of the alkylene group include methylene, ethylene, trimethylene, tetramethylene, pentamethylene, and hexamethylene. The preferable range of n is 1-18, more preferably 1-6.

X ^- is an anion, for example, fluorine,
Halogen ions of chlorine, bromine and iodine, carboxyl ions such as formic acid, acetic acid and oxalic acid, sulfate ions, phosphate ions, methyl or dimethyl phosphate ions, ethyl or diethyl phosphate ions, antimony fluoride ions, phosphorus fluoride ions, and fluorine ions. Arsenic ions, boron fluoride ions, perchlorate ions and the like are mentioned, and among them, halogen ions are preferable.

In the vinylbenzylphosphonium salt-based monomer represented by the above general formula (1), when ^one of R ^{1 to} R ³ is different from the same one, it is more preferable that ^one of R ^{1 to} R ³ is the same or different. Regardless, in the case of an alkyl group having 6 or more carbon atoms, particularly an alkyl group having a carbon number of at least octyl group is preferable because the antibacterial activity tends to be higher. Further, when n is 2 or more, even if the alkyl groups of R ^{1 to} R ³ are the same, the antibacterial activity becomes high, and excellent antibacterial activity is exhibited particularly at a lower concentration than at a high concentration. Is preferred. That is, it is considered that the antibacterial activity is increased at a low concentration by increasing the distance between the phosphonium base which is the active group and the main chain of the polymer.

Specific examples of the vinylbenzylphosphonium salt represented by the general formula (1) include, for example,
(Tri-n-butylphosphoniomethyl) styrene chloride, 4- (tri-n-octylphosphoniomethyl) styrene chloride, 4- (octadecyldimethylphosphoniomethyl) styrene chloride, 4- (2-tri-n-butylphosphonioethyl) ) Styrene chloride, 4- (2-
Tri-n-octylphosphonioethyl) styrene chloride, 4- (2-octadecyldimethylphosphonioethyl) styrene chloride, 4- (3-tri-n-butylphosphoniopropyl) styrene chloride, 4- (3-tri-n-octyl) Phosphoniopropyl) styrene chloride, 4- (4-tri-n-butylphosphoniobutyl) styrene chloride, 4- (4-tri-n-octylphosphoniobutyl) styrene chloride, 4- (5-tri-n-butylphosphonio) Pentyl) styrene chloride, 4-
(6-tri-n-butylphosphoniohexyl) styrene chloride, 4- (7-tri-n-butylphosphonioheptyl) styrene chloride, 4- (2-tri-n-butylphosphonioethyl) styrene bromide, 4- (3 -Tri-n-butylphosphoniopropyl) styrene bromide and the like, but are not limited thereto.

The method for producing the vinylbenzylphosphonium salt monomer represented by the general formula (1) is not particularly limited, and may be in accordance with a known production method. For example, a synthetic route represented by the following general formula (2) Can be manufactured.

[0017]

Embedded image

Wherein R ¹ , R ² , R ³ , X ^- and n
Is as defined above. )

That is, by reacting the styrene derivative (A) with the triorganophosphine (B) in the presence of an organic solvent and a polymerization inhibitor at a reaction temperature of 25 to 110 ° C., preferably at a boiling point of the solvent for at least 1 hour, The vinyl organobenzylphosphonium salt monomer represented by the general formula (1) can be easily obtained. Styrene derivative (A)
Is preferably used in an equimolar to 1 to 2 moles relative to the triorganophosphine (B). After completion of the reaction, the deposited precipitate may be filtered and ingested. Suitable organic solvents include n-hexane, toluene, and the like, and the amount used is not particularly limited.

The amount of the vinylbenzylphosphonium salt-based monomer represented by the above general formula (1) is preferably 0.1 to 4.0 mol% in the composition, more preferably 0.8 to 4.0 mol%.
3.0 mol% is preferred.

The antibacterial dental composition of the present invention contains a vinylbenzylphosphonium salt-based monomer represented by the above general formula (1) and a polymerizable monomer and a polymerization initiator as active ingredients. Is preferred.

The polymerizable monomer is not particularly limited as long as it is a monomer copolymerizable with the vinylbenzylphosphonium salt-based monomer represented by the above general formula (1). Esters with mono- or dihydric alcohols such as cyanoacrylic acid, (meth) acrylic acid, crotonic acid, cinnamic acid, sorbic acid, maleic acid, and itaconic acid; (meth) acrylamides such as N-isobutylacrylamide; Vinyl esters such as vinyl acetate; vinyl ethers such as butyl vinyl ether; mono-N-vinyl compounds such as N-vinylpyrrolidone; and styrene derivatives. Particularly, monofunctional monomers, difunctional and trifunctional (Meth) acrylic acid esters and urethane (meth) acrylic acid esters of polyfunctional monomers having a suitable property are preferred. Examples of the monofunctional monomer include methyl (meth) acrylate, n-propyl (meth) acrylate,
Isopropyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acrylate, (meth)
2-hydroxyethyl acrylate, siloxanyl (meth) acrylate, and the like. Examples of the bifunctional monomer include di (meth) acrylates such as propane diol, butane diol, hexane diol, octane diol, nonane diol, decane diol, and eicosane diol, ethylene glycol, diethylene glycol, triethylene glycol, and tetraethylene glycol. Di (meth) such as ethylene glycol, dodecaethylene glycol, tetradecaethylene glycol, propylene glycol, dipropylene glycol, tetradecapropylene glycol, etc.
Acrylates, glycerin (meth) acrylate,
2,2-bis [4- (3-methacryloyloxy-2-
Hydroxypropoxy) phenyl] propane, bisphenol A dimethacrylate, neopentyl glycol di (meth) acrylate, 2,2-di (4-methacryloxypolyethoxyphenyl) propane (ethoxy groups 2 to 10 in one molecule), 1, 2-bis (3-methacryloxy-
2-hydroxypropoxy) butane and the like. As the trifunctional monomer, a reaction of 2 moles of a (meth) acrylate monomer having a trimethylolpropane (meth) acrylate, pentaerythritol tetra (meth) acrylate, or urethane (meth) acrylate-based hydroxyl group with 1 mole of diisocyanate Product, both terminal NC
A reaction product of a urethane prepolymer of O and a (meth) acrylate monomer having a hydroxyl group is exemplified. The amount of these polymerizable monomers is not particularly limited,
The polymerizable monomers can be used alone or in combination of two or more.

Examples of the polymerization initiator include room temperature polymerization initiators such as 2,2-azobisisobutyronitrile, benzoyl peroxide and t-butyl hydroperoxide, camphorquinone, camphorquinone-tertiary amine, camphor. Quinone-peroxide, camphorquinone-aldehyde type, camphorquinone-mercaptan type, photopolymerization initiator such as acylphosphine oxide, and, when photopolymerization is performed by ultraviolet irradiation, benzoyl methyl ether, benzyldimethyl ketal, Benzophenone, 2
-Methylthioxanthone, diacetyl, benzyl, azobisisobutyronitrile, tetramethylthiuram disulfide and the like. The amount of these polymerization initiators is not particularly limited, and one or more of the polymerization initiators can be used as a mixture.

Further, the antibacterial dental composition of the present invention includes:
As other components of the above components, other antibacterial agents, organic polymers, fillers, stabilizers, coloring agents, polymerization inhibitors, fluorescent agents, ultraviolet absorbers and the like can be added. As the filler, for example, α-quartz, silica, alumina, hydroxyapatite, calcium carbonate, fluoroaluminosilicate glass, barium sulfate, titanium oxide, zirconia, glass, ultrafine silica, and an organic composite filler containing an organic component and an inorganic component And the like. Examples of the organic component of the organic composite filler containing an organic component and an inorganic component include polymethyl methacrylate, a copolymer of methyl methacrylate and a crosslinkable monomer, and a polymer powder such as polystyrene and polyvinyl chloride. As inorganic components, 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 , Synthetic silica, titanium silicate glass and the like. In addition, it is preferable to use an inorganic component after performing a surface treatment with an organic silicate compound or the like.

Further, the antibacterial dental polymer of the present invention comprises:
A composition comprising the vinylbenzylphosphonium salt-based monomer represented by the general formula (1) as an active ingredient, or
Further, it can be obtained by polymerizing a composition containing the above polymerizable monomer and a polymerizable initiator.

The polymerization method is not particularly limited, and any conventional polymerization method may be used. The above-mentioned dental antibacterial polymer can be easily obtained in a random, block or graft polymerization form by known means. For example, after a monomer copolymerizable with the vinylbenzylphosphonium salt-based monomer represented by the general formula (1) and a hydrophilic monomer as desired are dissolved in a desired solvent, polymerization is started. An agent may be added. The purpose of adding the hydrophilic monomer is to increase the solubility of the vinylbenzylphosphonium salt-based monomer in the solvent. Can be adjusted. As the hydrophilic monomer, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl acrylate, 3-hydroxypropyl methacrylate, N-
Vinylpyrrolidone, glycerol monomethacrylate,
Glycerol monoacrylate, N, N-dimethylmethacrylamide and the like can be mentioned.

As the solvent, for example, water, ethanol,
Dimethylformamide, benzene or a mixture thereof may be used. The reaction temperature and the reaction time depend on the type of the polymerization initiator, but are usually 20 to 150 ° C, preferably 40 to 100 ° C, and the reaction time is 0.5 hour or more, preferably 1 to 24 hours. The reaction is preferably performed in an inert atmosphere. After the reaction is completed, the reaction mixture is poured into a large amount of acetone, tetrahydrofuran, n-hexane, or the like, and the precipitate that precipitates is collected, whereby the dental antibacterial polymer according to the present invention can be obtained. The polymerization initiator may be added in an amount of usually 0.1 to 5 mol%, preferably 0.2 to 2 mol%, based on the concentration of the monomer. The degree of polymerization is mainly controlled by the type of the drug and the reaction conditions, and the higher the degree of antibacterial activity, the higher the degree of polymerization is preferable, but there is no particular limitation.
Furthermore, it can be made antibacterial by graft polymerization to another polymer material. For example, antimicrobial properties can be imparted to the surface of a polymer substrate such as polypropylene by photografting using benzophenone as a sensitizer and using a high-pressure mercury lamp. Further, a product obtained by homopolymerizing the vinylbenzylphosphonium salt-based monomer used in the present invention can be used as an antibacterial dental material by kneading it into a thermoplastic resin such as polysulfone or polycarbonate.

The antibacterial dental polymer of the present invention can be used as a dental composite range, backing material, dental adhesive, denture base range, denture lining material, dental coating material, dental range cement, small scale It can be suitably used as a fissure filling material, a temporary restoration range, or the like.

[0029]

The present invention will be described in detail below, but the present invention is not limited thereto. Examples 1 to 4 Methyl methacrylate and 2-hydroxyethyl methacrylate were mixed at a molar ratio of 8 to 2, and the amount of 4- (tri-n-butylphosphonio) shown in Table 1 was determined based on the mixed monomer. Methyl) styrene chloride (hereinafter, V) was mixed and dissolved in water. Then, 0.5% by weight of the benzoyl peroxide mixed monomer was added, and the
sealed in a glass tube at 55 ° C. for 20 hours, then 10
Polymerization was performed at 0 ° C. for 2 hours to obtain an antibacterial dental polymer.
The antibacterial properties and mechanical properties of the antibacterial dental polymer were evaluated by the following methods. The results are shown in Tables 1 and 2.

Comparative Examples 1 and 2 Example 1 was repeated except that the amount of ethyltrimethylammonium methacrylate (hereinafter referred to as M) shown in Table 1 was used in place of 4- (tri-n-butylphosphoniomethyl) styrene chloride. The antibacterial dental polymer was obtained in the same manner as in Nos. 1 to 4, and the same evaluation was performed. Table 1 shows the results
And Table 2.

(Evaluation of antibacterial activity) Test bacteria and cultured Brain supplemented with 0.5% yeast extract of S. mutans.
After inoculation the Heaet Infusion Broth (hereinafter BHI) medium _{3mL, CO 2 15%, H} 2 15%, under anaerobic conditions of the N ₂ 70%, 37 ℃, was 24 hours, and pre-cultured Kin'eki. On the other hand, as a culture solution for an antibacterial test, BHI supplemented with 0.5% yeast extract and 5% sucrose was separately prepared in order to promote the growth of S. mutans. The antibacterial polymer used in the antibacterial test was a polymer in a glass tube having a diameter of 10 mm and a thickness of 1 mm by Isomet (manufactured by Buehra).
It was cut into mm to obtain a disc-shaped test piece. Then, a hole for suspension of about 0.5 mm was made in the corner of the disc-shaped test piece with a dental hand engine, and under water injection, water-resistant emery paper # 1.
After polishing to 500 μm and further to a wrapping film of 3 μm (manufactured by Maruto) and then polishing to 0.3 μm, it was washed with distilled water in an ultrasonic cleaner. These specimens were then
After sterilizing with 0% ethanol, it was stored in sterilized distilled water and used for experiments. Each test piece was suspended with a 0.5 mm correction wire, immersed in a solution obtained by adding 60 μL of the precultured bacterial solution to 3 mL of a sucrose-containing culture solution, and anaerobically cultured at 37 ° C. for 24 hours. -Measurement of the amount of adherent bacteria After the anaerobic cultivated test piece was washed with distilled water, the amount of bacteria remaining on the sample surface was defined as the amount of adherent bacteria. That is, the test piece after washing with water was immersed in a 0.3% crystal violet solution for 60 seconds to color the bacteria, washed thoroughly with water, poured into a test tube containing 1 mL of ethanol, and the dye was eluted. Was used to measure the transmittance at 600 nm. For comparison, an antimicrobial polymer containing V and M and containing methyl methacrylate and 2-hydroxyethyl methacrylate at a molar ratio of 8 to 2 was used as a control.

[0032]

[Table 1]

(Evaluation of Mechanical Properties) The antibacterial dental polymer obtained in Examples 1 to 4 was used for compression test with a diameter of 4 mm.
mm, length 10mm, diameter 4mm, length 25 for bending test
Samples were prepared by cutting into mm. The test machine used was an autograph AGS-500 manufactured by Shimadzu Corporation, the crosshead speed was 2 mm / min in the compression test and 1 mm / min in the bending test, and the flexural modulus was 2 to 2 of the stress-strain curve of the bending test.
The calculation was performed using a load range of 10 kgf.

[0034]

[Table 2]

Examples 1 to 4 all exhibited higher antibacterial activities than Comparative Examples 1 and 2 and the control. Further, the mechanical properties of Examples 1 to 4 were slightly inferior to those of the control, but were sufficient for practical use.

[0036]

The antibacterial dental polymer of the present invention is a non-eluting antibacterial polymer, and its antibacterial properties are not only sustainedly expressed only on the surface of the dental polymer, but also important for caries. Streptococcus Mutan
Since the antibacterial activity against s) is very high, its value as an antibacterial dental polymer for dental range materials is extremely large.

Claims (3)

[Claims] 1. An antibacterial agent represented by the following general formula (1): (Wherein R ¹ , R ² and R ³ are the same or different and are each a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, an aryl group, an aralkyl group, a hydroxy group or an alkoxy group. Represents an alkyl group, an aryl group or an aralkyl group substituted by X, X ⁻ represents an anion, and n represents an integer of 1 or more.) An antibacterial dental composition comprising: 2. The antibacterial dental composition according to claim 1, further comprising a polymerizable monomer and a polymerization initiator as active ingredients. 3. An antibacterial dental polymer obtained by polymerizing the antibacterial dental composition according to claim 1 or 2.