JP3615802B2 - Antibacterial monomers and their synthesis - Google Patents

Description

【０００９】
（Ｒ^１ は−Ｈ又は−ＣＨ_３ を表わす）
で示される構造を有する（メタ）アクリロイルアミノフェニル硼酸を主要な成分とするものである。
【００１０】
このような（メタ）アクリロイルアミノフェニル硼酸としては、２−（メタクリロイルアミノ）フェニル硼酸、３−（メタクリロイルアミノ）フェニル硼酸、及び４−（メタクリロイルアミノ）フェニル硼酸、２−（アクリロイルアミノ）フェニル硼酸、３−（アクリロイルアミノ）フェニル硼酸、及び４−（アクリロイルアミノ）フェニル硼酸がある。
【００１１】
これらの（メタ）アクリロイルアミノフェニル硼酸は、例えば、２−、３−、又は４−アミノフェニル硼酸と（メタ）アクリル酸クロリドとの反応によって得られる。この反応を下の式（ＩＩ）に示す。
【００１２】
【化３】

【００１３】
（Ｒ^１ は−Ｈ又は−ＣＨ_３ を表わす）
【００１４】
【発明の効果】
本発明の（メタ）アクリロイルアミノフェニル硼酸は、グラム陰性菌、グラム陽性菌のいずれに対しても抗菌性を有し、且つ、歯科用接着剤や充填剤の主成分である（メタ）アクリル酸やこれらのエステル等と通常のラジカル重合により共重合可能である。従って、本発明の（メタ）アクリロイルアミノフェニル硼酸を添加することにより、歯科用接着剤や充填剤に半永久的に抗菌性を付与することができる。
【００１５】
【実施例】
以下、本発明について実施例を用いて具体的に説明する。
【００１６】
［実施例１］
３−（メタクリロイルアミノ）フェニル硼酸の合成
滴下漏斗及びコンデンサーを備えた二口フラスコ（２００ｍｌ）に、３−アミノフェニル硼酸（１．８６ｇ、０．０１ｍｏｌ）と水６１ｍｌを入れ、良く撹拌した後、炭酸水素ナトリウム（５．０ｇ、０．０６ｍｏｌ）を少量づつ加えた。次に滴下漏斗よりメタクリル酸クロリド（１．２ｍｌ、０．０１２３ｍｏｌ）を一滴づつ室温で約１５分で加えた。撹拌を十分に行いながら反応を更に３時間行うと全体が白濁してきた。
【００１７】
反応終了後、ガラスフィルターで生成物を濾別し、乾燥した。収量は１．４ｇであった。濾液を濃塩酸で酸性にし、２４時間静置すると、結晶０．３ｇが得られた。生成物１．４ｇを沸騰水３０ｍｌに溶かし、濾過により不溶分を除いた。濾液に濃塩酸１０ｍｌを加えて酸性にすると、白色の３−（メタクリロイルアミノ）フェニル硼酸の針状結晶１．２ｇが得られた。得られた結晶について、元素分析、赤外線吸収スペクトル測定及び^１ Ｈ−ＮＭＲ測定を行った。結果は以下の通りであった。
【００１８】
元素分析
実測値（Ｃ_１０Ｈ_１３ＢＮＯ_３ として）：
Ｃ，５８．５９ｗｔ％ ； Ｈ，５．９０ｗｔ％ ； Ｎ，６．８３ｗｔ％
計算値：Ｃ，５８．５８ｗｔ％ ； Ｈ，６．０６ｗｔ％ ； Ｎ，６．８７ｗｔ％
赤外線吸収スペクトル
（株式会社日立製作所製、Ｉ−５０２０ＦＴ−ＩＲ使用、ＫＢｒ法で測定）
ν ３３１０−３４２０ｃｍ^−１（ＮＨ，ＯＨ），１６５８ｃｍ^−１（Ｃ＝Ｏ），１６２４ｃｍ^−１（Ｃ＝Ｃ）
^１ Ｈ−ＮＭＲスペクトル（株式会社日立製作所製、Ｉ−２４０使用、測定周波数６０ＭＨｚ、測定溶媒はＣＤＣｌ_３ ＋ＤＭＳＯ−ｄ_６ 使用）
α−ＣＨ_３ ＝２．０ｐｐｍ（ｓ，３Ｈ），ＣＨ_２ ＝５．４ｐｐｍ，５．８５ｐｐｍ（ｄ，２Ｈ），ｐｈｅｎｙｌ＝７．２２−７．８８ｐｐｍ（ｔｔ，ｄ，ｄ，ｓ，４Ｈ），９．４ｐｐｍ（ｓ，１Ｈ）．
尚、赤外線吸収スペクトル及び^１ Ｈ−ＮＭＲスペクトルについては各々図１及び図２に示す。
【００１９】
得られた３−（メタクリロイルアミノ）フェニル硼酸について、次に抗菌性を調べた。抗菌性の測定には濾紙法を用いた。
【００２０】
先ず、予め培養した３種類の細菌、Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｍｕｔａｎｓ、Ｌａｃｔｏｂａｃｉｌｌｕｓ ｃａｓｅｉ 及びＡｃｔｉｎｏｍｙｓｅｓ ｖｉｓｃｏｓｕｓを各々寒天に加えて、この寒天を固まらせた。次いで、これらの寒天の各々に、３−（メタクリロイルアミノ）フェニル硼酸の５％又は１０％ＤＭＳＯ溶液を染み込ませた直径６ｍｍの濾紙を置き、３７℃で１２時間培養し、細菌発育阻止帯の幅を測定した。対照群として、ＤＭＳＯのみを用いた場合についても、同様にして測定した。結果を表１に示す。
【００２１】
【表１】

【００２２】
表１の結果から、ＤＭＳＯのみを用いた場合に比べ、３−（メタクリロイルアミノ）フェニル硼酸の５％あるいは１０％ＤＭＳＯ溶液を用いた場合のほうが、上記３種の細菌のいずれに対しても細菌発育阻止帯が広くなっていた。
【００２３】
このことから、３−（メタクリロイルアミノ）フェニル硼酸が上記３種の細菌に対し抗菌性を有することが判る。
【図面の簡単な説明】
【図１】実施例１で得られた３−（メタクリロイルアミノ）フェニル硼酸の赤外線吸収スペクトル。
【図２】実施例１で得られた３−（メタクリロイルアミノ）フェニル硼酸の６０ＭＨｚ ^１Ｈ−ＮＭＲスペクトル。[0001]
[Industrial application fields]
The present invention relates to an antibacterial monomer that has antibacterial properties and can also be a monomer copolymerizable with (meth) acrylic acid or an ester thereof.
[0002]
[Prior art]
Borate salts such as sodium borate have been conventionally used as antiseptics, bacteriostatic agents, wound cleansing agents, gargles (oral cleansing agents) and the like.
[0003]
In addition, boric acid is known to form an ester-type complex ion with a polyhydric alcohol, particularly an alcohol having two hydroxyl groups in the cis position, and exhibits a weak bactericidal action.
[0004]
[Problem to be Solved by the Invention]
Therefore, a boric acid compound, for example, a salt of an ester type complex ion formed from boric acid and a polyhydric alcohol shown above is mixed with a dental adhesive or filler made of a mixture of (meth) acrylic acid ester, It is conceivable to impart antibacterial properties to these dental adhesives and fillers.
[0005]
However, since many of the boric acid compounds that can be used as bactericides and bacteriostatic agents are solid at room temperature, it is difficult to uniformly mix them with dental adhesives and fillers. In addition, since dental adhesives and fillers are used in a constantly moist environment in the oral cavity, borate and ester complex ions of boric acid and polyhydric alcohol are easily dissolved from the cured adhesives and fillers. There was a problem that the antibacterial effect did not last long.
[0006]
An object of the present invention is to solve the above-mentioned problems by providing an antibacterial monomer copolymerizable with (meth) acrylic acid or an ester thereof.
[0007]
[Means for solving problems]
The antibacterial monomer of the present invention has the following formula (I)
[0008]
[Chemical 2]

[0009]
(R ¹ represents —H or —CH ₃ )
The main component is (meth) acryloylaminophenyl boric acid having a structure represented by:
[0010]
As such (meth) acryloylaminophenyl boric acid, 2- (methacryloylamino) phenyl boric acid, 3- (methacryloylamino) phenyl boric acid, 4- (methacryloylamino) phenyl boric acid, 2- (acryloylamino) phenyl boric acid, There are 3- (acryloylamino) phenyl boric acid and 4- (acryloylamino) phenyl boric acid.
[0011]
These (meth) acryloylaminophenyl boric acids are obtained, for example, by reacting 2-, 3-, or 4-aminophenyl boric acid with (meth) acrylic acid chloride. This reaction is shown below in formula (II).
[0012]
[Chemical 3]

[0013]
(R ¹ represents —H or —CH ₃ )
[0014]
【The invention's effect】
The (meth) acryloylaminophenyl boric acid of the present invention has antibacterial properties against both gram-negative bacteria and gram-positive bacteria, and (meth) acrylic acid is a main component of dental adhesives and fillers And these esters can be copolymerized by ordinary radical polymerization. Therefore, by adding the (meth) acryloylaminophenyl boric acid of the present invention, antibacterial properties can be imparted semi-permanently to dental adhesives and fillers.
[0015]
【Example】
Hereinafter, the present invention will be specifically described with reference to examples.
[0016]
[Example 1]
Synthesis of 3- (methacryloylamino) phenyl boric acid In a two-necked flask (200 ml) equipped with a dropping funnel and a condenser, 3-aminophenyl boric acid (1.86 g, 0.01 mol) and 61 ml of water were placed and stirred well. Sodium bicarbonate (5.0 g, 0.06 mol) was added in small portions. Next, methacrylic acid chloride (1.2 ml, 0.0123 mol) was added dropwise from the dropping funnel at room temperature in about 15 minutes. When the reaction was further carried out for 3 hours with sufficient stirring, the whole became cloudy.
[0017]
After completion of the reaction, the product was filtered off with a glass filter and dried. The yield was 1.4g. The filtrate was acidified with concentrated hydrochloric acid and allowed to stand for 24 hours to obtain 0.3 g of crystals. 1.4 g of the product was dissolved in 30 ml of boiling water, and the insoluble matter was removed by filtration. When the filtrate was acidified with 10 ml of concentrated hydrochloric acid, 1.2 g of white 3- (methacryloylamino) phenylboric acid needle crystals were obtained. Elemental analysis, infrared absorption spectrum measurement, and ¹ H-NMR measurement were performed on the obtained crystals. The results were as follows.
[0018]
Elemental analysis measured values (as C ₁₀ H ₁₃ BNO ₃ ):
C, 58.59 wt%; H, 5.90 wt%; N, 6.83 wt%
Calculated value: C, 58.58 wt%; H, 6.06 wt%; N, 6.87 wt%
Infrared absorption spectrum (manufactured by Hitachi, Ltd., using I-5020FT-IR, measured by KBr method)
ν 3310-3420 cm ⁻¹ (NH, OH), 1658 cm ⁻¹ (C═O), 1624 cm ⁻¹ (C═C)
¹ H-NMR spectrum (manufactured by Hitachi, Ltd., using I-240, measuring frequency 60 MHz, measuring solvent using CDCl ₃ + DMSO-d ₆ )
α-CH ₃ = 2.0 ppm (s, 3H), CH ₂ = 5.4 ppm, 5.85 ppm (d, 2H), phenyl = 7.22-7.88 ppm (tt, d, d, s, 4H) , 9.4 ppm (s, 1 H).
The infrared absorption spectrum and ¹ H-NMR spectrum are shown in FIGS. 1 and 2, respectively.
[0019]
The obtained 3- (methacryloylamino) phenyl boric acid was then examined for antibacterial properties. The filter paper method was used for the measurement of antibacterial properties.
[0020]
First, three types of bacteria previously cultured, Streptococcus mutans, Lactobacillus casei, and Actinomyces viscosus were each added to agar to solidify the agar. Next, a filter paper having a diameter of 6 mm soaked with 5% or 10% DMSO solution of 3- (methacryloylamino) phenyl boric acid was placed on each of these agars and cultured at 37 ° C. for 12 hours. Was measured. As a control group, the same measurement was performed when only DMSO was used. The results are shown in Table 1.
[0021]
[Table 1]

[0022]
From the results shown in Table 1, it was found that the use of a 5% or 10% DMSO solution of 3- (methacryloylamino) phenylboric acid compared to the case of using only DMSO against the above three types of bacteria. The stunt zone was wide.
[0023]
This shows that 3- (methacryloylamino) phenyl boric acid has antibacterial properties against the above three types of bacteria.
[Brief description of the drawings]
1 is an infrared absorption spectrum of 3- (methacryloylamino) phenyl boric acid obtained in Example 1. FIG.
2 is a 60 MHz ¹ H-NMR spectrum of 3- (methacryloylamino) phenyl boric acid obtained in Example 1. FIG.

Claims (3)

Formula (I):

(R ₁ represents —H or —CH ₃ )
A dental antibacterial agent comprising (meth) acryloylaminophenyl boric acid having a structure represented by: Formula (I):

(R ₁ represents —H or —CH ₃ )
A dental material which is a mixture or copolymer of (meth) acryloylaminophenyl boric acid and (meth) acrylic acid or an ester thereof having a structure represented by: Formula (I):

(R ₁ represents —H or —CH ₃ )
A method for imparting antibacterial properties to a dental material, comprising mixing or copolymerizing (meth) acryloylaminophenyl boric acid having a structure represented by the formula (meth) acrylic acid or an ester thereof.

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