JP2011051941A - Antimicrobial composition for oral cavity use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antimicrobial composition for oral cavity use, having an antimicrobial effect not only in a dental prosthesis but also in a wide area in the oral cavity and high curability and forming a film for a long period of time. <P>SOLUTION: The antimicrobial composition for oral cavity use includes 15-70 wt.% of a monofunctional (meth)acrylate compound not containing an acid group, 15-70 wt.% of a polyfunctional (meth)acrylate compound not containing an acid group, 1-20 wt.% of a (meth)acrylate compound containing an acid group, 0.01-10 wt.% of a polymerization initiator and 0.001-10 wt.% of chlorhexidine and/or its compound. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an antibacterial composition for oral cavity that is applied to a tooth surface or a prosthesis as a dental coating material.

  Caries occur when enamel is dissolved by acids produced by bacteria in the oral cavity. Among them, the mutans bacterium is cited as an important causative bacterium of caries. Periodontitis, a disease of periodontal tissue, is also said to develop due to oral bacteria. In order to prevent these diseases, it is important to promptly remove plaque formed by bacteria in the oral cavity, and tooth brushing is mainly recommended. Furthermore, it is important to strengthen the tooth structure and prevent the formation of plaque on the tooth surface.

  As a method for strengthening teeth, an acid fluorophosphate solution, a fluorinated diamine silver solution, or the like is generally applied to the tooth surface to improve the acid resistance of the enamel. On the other hand, some attempts have been made to prevent the formation of plaque, depending on the type of material used, including the addition of antibacterial agents to dental restoration materials such as dental composite resins and dental cement, There is a method using an antibacterial composition that is applied to a surface or oral cavity (see, for example, Non-Patent Documents 1 and 2, and Patent Documents 1 to 11).

  However, simply adding the antibacterial agent to the dental restorative material only elutes the antibacterial agent from around the dental material in the oral cavity, which is not satisfactory in terms of the antibacterial effect. Moreover, the original property of the dental restorative material may be deteriorated by blending the antibacterial agent. Therefore, an antibacterial composition to be applied to the tooth surface and the prosthetic surface was developed as a composition to be applied not only to the periphery of the dental restoration material containing the antibacterial agent but also to a wider range of tooth surfaces and oral cavity. . However, the antibacterial composition of the type to be applied in this way has a problem that it has a low retention in the oral cavity and cannot give an antibacterial action for a long time, and an antibacterial composition using a polymerizable compound such as methacrylate Even if it is a thing, there existed a problem that the coating surface received the superposition | polymerization inhibition by oxygen and sclerosis | hardenability became low and an antibacterial composition peeled from a tooth surface, a dental prosthesis, etc. with time.

Takemura Kinzo, Journal of the Japan Dental Conservation Society, Vol. 26, No. 2, 540-547, 1983 Masaaki Iwahisa et al., Japanese Journal of Dentistry Conservation, Vol. 30, No. 5, 1444-1448, 1987 Japanese Patent Laid-Open No. 4-189661 JP-A-4-346905 Japanese Patent Laid-Open No. 5-126398 JP-A-5-015435 JP-A-6-192060 Japanese Patent Laid-Open No. 7-206621 JP 7-215814 A JP-T-2006-507361 JP-T-2006-505303 Japanese Patent Laid-Open No. 2007-254300 Japanese Patent Application Laid-Open No. 2007-269637

  Therefore, the present invention provides an antibacterial composition for oral cavity that can provide an antibacterial effect not only in a dental restorative material but also in a wide range in the oral cavity and can form a film for a long period of time with high curability. Let it be an issue.

  As a result of intensive studies to solve the above problems, the present inventors have found that a monofunctional (meth) acrylate compound having no acid group, a polyfunctional (meth) acrylate compound not having an acid group, and having an acid group The present invention has been completed by finding that the above problems can be solved by using an antibacterial composition for oral cavity composed of a (meth) acrylate compound, a photopolymerization catalyst, chlorhexidine and / or a compound thereof.

  Since the antibacterial composition for oral cavity according to the present invention has excellent curability and long-term durability, it can maintain antibacterial properties for a long period of time.

  The monofunctional (meth) acrylate compound having no acid group in the present invention means a monomer, oligomer, or prepolymer having one (meth) acryloyl group in acrylate or methacrylate. Specific examples of monofunctional (meth) acrylate compounds having no acid group used in the present invention include methyl (meth) acrylate, ethyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl (meth) acrylate, and isobutyl. (Meth) acrylate, hydroxypropyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, glycidyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) ) Acrylate, 2-methoxyethyl (meth) acrylate, 2-ethoxyethyl (meth) acrylate, 2-methoxyethyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, benzyl (meth) acrylate There can be exemplified. Of these, methyl methacrylate is most preferred in view of safety and volatility.

  The amount of the monofunctional (meth) acrylate compound having no acid group used in the present invention needs to be 15 to 70% by weight in consideration of the drying property of the coated surface and the strength after curing. If it is less than% by weight, the drying property and strength on the surface are lowered, and if it exceeds 70% by weight, the curability of the surface is lowered.

  The polyfunctional (meth) acrylate compound having no acid group is a polyfunctional (meth) acrylate compound having two or more (meth) acryloyl groups in one molecule and acts as a crosslinking agent. As this compound, 2-hydroxy-1,3-di (meth) acryloxypropane, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, butylene glycol di (meth) ) Acrylate, neopentyl glycol di (meth) acrylate, 1,3-butanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, 1,6-hexanediol di (meth) acrylate, trimethylol Propane tri (meth) acrylate, trimethylolethane tri (meth) acrylate, pentaerythritol tri (meth) acrylate, trimethylolmethane tri (meth) acrylate, pentaerythritol tetra (meth) acrylate Dipentaerythritol tetra (meth) acrylate, dipentaerythritol penta (meth) acrylate, dipentaerythritol hexa (meth) acrylate, 1,3,5-tris (1,3-bis ((meth) acryloyloxy) -2- Examples thereof include propoxycarbonylaminohexane) -1,3,5- (1H, 3H, 5H) triazine-2,4,6-trione.

  Since the polyfunctional (meth) acrylate compound having no acid group is a monomer having a plurality of (meth) acryloyl groups acting as a crosslinking agent, it is preferable to select a monomer having a large number of polymerization reactive groups. A polyfunctional (meth) acrylate monomer having four or more polymerizable groups in one molecule such as pentaerythritol (meth) acrylate or dipentaerythritol (meth) acrylate is preferable. Specifically, pentaerythritol tetra (meth) acrylate, dipentaerythritol tetra (meth) acrylate, dipentaerythritol penta (meth) acrylate, dipentaerythritol hexa (meth) acrylate, 1,3,5-tris (1, One or two selected from 3-bis ((meth) acryloyloxy) -2-propoxycarbonylaminohexane) -1,3,5- (1H, 3H, 5H) triazine-2,4,6-trione In view of operability and safety, dipentaerythritol hexa (meth) acrylate, 1,3,5-tris (1,3-bis ((meth) acryloyloxy) -2-propoxycarbonyl Aminohexane) -1,3,5- (1H, 3H, 5H) triazine-2,4,6- Rion is most preferable.

  The compounding amount of the polyfunctional (meth) acrylate compound having no acid group used in the present invention needs to be 15 to 70% by weight, and if it is less than 15% by weight, the effect of crosslinking cannot be obtained and after curing. When the strength of the composition is less than 70% by weight, the viscosity of the composition is too high and the operability (applicability) is lowered.

  The antibacterial composition for oral cavity according to the present invention contains a (meth) acrylate compound having an acid group in order to strongly adhere to a tooth surface or a prosthesis surface. The (meth) acrylate compound having an acid group is preferably a (meth) acrylate having a phosphate group or a carboxyl group, and a (meth) acrylate having one or more phosphate groups or carboxyl groups in one molecule. Can be used. The (meth) acrylate having an acid group is preferably blended in the composition in an amount of 1 to 20% by weight, and if it is less than 1% by weight, the adhesive strength is insufficient. Decreases. Since the phosphoric acid group has a stronger acidity than the carboxyl group, the effect of dissolving the smear layer on the tooth surface and the demineralization of the tooth is high, and particularly shows a high adhesion to the tooth.

  Examples of the (meth) acrylate compound having a phosphoric acid group include 2- (meth) acryloyloxyethyl dihydrogen phosphate, bis [2- (meth) acryloyloxyethyl] hydrogen phosphate, 2- (meth) acryloyloxyethylphenyl Hydrogen phosphate, 6- (meth) acryloyloxyhexyl dihydrogen phosphate, 6- (meth) acryloyloxyhexyl phenyl hydrogen phosphate, 10- (meth) acryloyloxydecyl dihydrogen phosphate, 1,3-di (meth) ) Acryloylpropane-2-dihydrogen phosphate, 1,3-di (meth) acryloylpropane-2-phenylhydrogen phosphate, bis [5- {2- (meth) acryloyloxy Ethoxycarbonyl} heptyl] hydrogen phosphate, and the like. Among these, 10- (meth) acryloyloxydecyl dihydrogen phosphate is particularly preferable from the viewpoints of adhesiveness and stability of (meth) acrylate itself. These (meth) acrylate compounds having a phosphoric acid group may be used alone or in admixture of two or more.

  Examples of the (meth) acrylate having a carboxyl group include 4- (meth) acryloxyethyl trimellitic acid, 4- (meth) acryloxyethyl trimellitic anhydride, 4- (meth) acryloxydecyl trimellitic acid, 4 -(Meth) acryloxydecyl trimellitic anhydride, 11- (meth) acryloyloxy-1,1-undecanedicarboxylic acid, 1,4-di (meth) acryloyloxypyromellitic acid, 2- (meth) acryloyloxy Examples thereof include ethyl maleic acid, 2- (meth) acryloyloxyethyl phthalic acid, and 2- (meth) acryloyloxyethyl hexahydrophthalic acid. Among these, 4- (meth) acryloxyethyl trimellitic acid and 4- (meth) acryloxyethyl trimellitic anhydride are particularly preferable from the viewpoint of adhesive strength.

  The antibacterial composition for oral cavity according to the present invention uses a known photopolymerization catalyst system. As the photopolymerization catalyst, a combination of a photosensitizer and a reducing agent is generally used. As the photosensitizer, camphorquinone, benzyl, diacetyl, benzyldimethyl ketal, benzyl diethyl ketal, benzyl di (2-methoxyethyl) ketal are used. 4,4′-dimethylbenzyl-dimethyl ketal, anthraquinone, 1-chloroanthraquinone, 2-chloroanthraquinone, 1,2-benzanthraquinone, 1-hydroxyanthraquinone, 1-methylanthraquinone, 2-ethylanthraquinone, 1-bromoanthraquinone Thioxanthone, 2-isopropylthioxanthone, 2-nitrothioxanthone, 2-methylthioxanthone, 2,4-dimethylthioxanthone, 2,4-diethylthioxanthone, 2,4-diisopropylthioxanthone, 2 Chloro-7-trifluoromethylthioxanthone, thioxanthone-10,10-dioxide, thioxanthone-10-oxide, benzoin methyl ether, benzoin ethyl ether, isopropyl ether, benzoin isobutyl ether, benzophenone, bis (4-dimethylaminophenyl) ketone, 4,4 Examples include '-bisdiethylaminobenzophenone, acylphosphine oxides such as (2,4,6-trimethylbenzoyl) diphenylphosphine oxide, and compounds containing an azide group, which can be used alone or in combination.

  A tertiary amine or the like is generally used as the reducing agent. Tertiary amines include N, N-dimethyl-p-toluidine, N, N-dimethylaminoethyl methacrylate, triethanolamine, methyl 4-dimethylaminobenzoate, ethyl 4-dimethylaminobenzoate, isoamyl 4-dimethylaminobenzoate. Is preferred. Other reducing agents include benzoyl peroxide, sodium sulfinate derivatives, organometallic compounds, etc., which can be used alone or in combination.

  Chlorhexidine and / or a compound thereof is blended to give an antibacterial effect to the oral antibacterial composition. There are chlorhexidine, chlorhexidine (gluconate), chlorhexidine (hydrochloride), chlorhexidine (acetate), etc., which can be used alone or in combination. Chlorhexidine and / or its compound is preferably blended in the antibacterial composition for oral cavity in an amount of 0.001 to 10% by weight, and if it is less than 0.001% by weight, the antibacterial effect is insufficient and exceeds 10% by weight. And adversely affects the curability of the composition. In order to sufficiently exhibit the antibacterial effect in the oral cavity, it may be 0.5 to 10% by weight, further 1 to 10% by weight.

  In the antibacterial composition for oral cavity according to the present invention, a filler component may be blended within a range that does not impair the effects of the main components described above. The filler component has the effect of increasing the strength of the composition. Fillers include silicic anhydride, barium glass, alumina glass, potassium glass, fluoroaluminosilicate glass, synthetic zeolite, calcium phosphate, feldspar, fumed silica, aluminum silicate, calcium silicate, magnesium carbonate, hydrous silicic acid There are various powders such as hydrous calcium silicate, hydrous aluminum silicate and quartz. These fillers can be combined with (meth) acrylate compounds such as γ-methacryloxypropyltrimethoxysilane, vinyltrichlorosilane, vinyltriethoxysilane, vinyltrimethoxysilane, vinyltriacetoxysilane, vinyltri (methoxyethoxy) silane, etc. Surface treatment may be performed with a silane coupling agent. In addition, an organic-inorganic composite filler prepared by previously mixing the above filler with a monomer or oligomer and curing it, and then pulverizing it can also be used. These fillers can be used alone or in admixture of two or more. Among these, fumed silica has a fine particle size and is effective in adjusting the fluidity of the composition in a small amount.

  It goes without saying that the antibacterial composition for oral cavity according to the present invention can be appropriately mixed with a polymerization inhibitor, a pigment, a fluorescent agent and the like which are usually used as necessary.

  An antibacterial composition for oral cavity was prepared according to the formulation (% by weight) shown in Table 1, and the adhesiveness to the tooth surface, curing characteristics, and antibacterial properties were evaluated.

Abbreviations in Table 1 are as follows.
MMA: Methyl methacrylate EMA: Ethyl methacrylate UDMA: Urethane dimethacrylate (di-2-methacryloxyethyl-2,2,4-trimethylhexamethylene dicarbamate)
Bis-GMA: bisphenol A diglycidyl methacrylate DPHA: dipentaerythritol hexamethacrylate 10-M: 10-methacryloyloxydecyl dihydrogen phosphate Bis-HP: bis [2-methacryloyloxyethyl] hydrogen phosphate 2-MHP: 2- Methacryloyloxyethyl dihydrogen phosphate 4-META: 4-methacryloxyethyl trimellitic anhydride

Aerosil: Fumed silica (trade name R812, manufactured by Nippon Aerosil Co., Ltd.)

246TMB: (2,4,6-trimethylbenzoyl) diphenylphosphine oxide 4-AE: ethyl 4-dimethylaminobenzoate

<Adhesion confirmation test>
A disk-shaped cured body (diameter: 15 mm, height: 1.5 mm) made with glass ionomer cement for filling and repairing (trade name: Fuji IXGP Fast Capsule, manufactured by GC Corporation) is stored in distilled water at 37 ° C. for 24 hours. To do. A plastic tape having a diameter of 3 mm and a thickness of 0.1 mm is pasted on the cured body to regulate the adhesion area. The polymerizable composition of each example and comparative example was applied to the surface to which the area was regulated, and cured by irradiating light for 20 seconds with a dental optical illuminator (trade name: G-light, manufactured by GC Corporation). Thereafter, the stainless steel rod for the tensile test jig was hardened with a glass polyalkenoate resin cement (trade name: FUJI LUTE, manufactured by GC Corporation) for dental use. It was stored in an incubator at 37 ° C. and 100% humidity for 1 hour, and then immersed in distilled water at 37 ° C. 24 hours after the start of kneading, the crosshead speed was 1 mm / min. A tensile test was conducted at The results are shown in Table 1.

<Curability confirmation test>
One drop of the composition is dropped on black kneaded paper (No. 14B) that does not react with the composition, and light irradiation is performed for 20 seconds with a dental light illuminator (trade name: G-Light, manufactured by GC Corporation) to cure the surface. The state (stickiness) was confirmed with a finger. The results are shown in Table 1.

<Strength test of cured body>
One drop of the composition was dropped on a black kneaded paper (product name No. 14B, manufactured by GC Corporation) that did not react with the antibacterial composition for oral cavity according to the present invention, and a dental luminaire (trade name: G-light, GC). For 20 seconds. The cured body was pushed with a plastic spatula, and the strength of the cured body was confirmed. The results are shown in Table 1.

<Antimicrobial confirmation test>
Streptococcus mutans bacteria were cultured in a liquid medium, and a BHI agar medium supplemented with 1% by weight thereof was prepared at 10 to 15 mL / dish. An acrylic disk (φ10 mm × 1 mm) coated and photocured with the composition and an uncoated acrylic disk as a control were placed on an agar medium. After culturing at 37 ° C. in an aerobic environment for 2 days and removing the acrylic disc, the diameter (average of the longest part and the shortest part) and depth of the inhibition circle were measured. The results are shown in Table 1.

<Table 1>

Claims (1)

Monofunctional (meth) acrylate compound having no acid group: 15 to 70% by weight,
Polyfunctional (meth) acrylate compound having no acid group: 15 to 70% by weight,
(Meth) acrylate compound having an acid group: 1 to 20% by weight,
Polymerization initiator: 0.01 to 10% by weight,
Chlorhexidine and / or its compound: 0.001 to 10% by weight,
An antibacterial composition for oral cavity composed of