JPH09249624A - Benzylammnium derivative and dental treating material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a benzylammnium derivative useful as a dental material such as a dental tooth, having antimicrobial action capable of suppressing adhesion and proliferation of microorganisms, having bonding action and permeability and adhesiveness to dentin. SOLUTION: This benzylammnium derivative is shown by formula I ((n) is the number of methylene side-chains and 1-20; X is a halogen). The compound of formula I is obtained by heating a dicarboxylic acid of formula II under reflux to give a dicarboxylic acid ester, saponifying the ester, adding a proper solvent to the ester to give a precipitate and collecting the precipitate by filtration. Water and an acid are added to the precipitate to give a compound of formula III. Further the compound of formula III is converted into N,N- dimethylamino-alcohol, which is heated with a benzyl halide, a solidified crude reaction product is recrystallized with ethanol to give a compound of formula IV, which is further separated and purified.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a benzylammonium derivative used as a dental additive and a dental treatment material formed by adding the benzylammonium derivative.

[0002]

[Problems to be Solved by the Invention] In dental treatment,
BACKGROUND ART Various dental treatment materials (in the field of dentistry, referred to as "resin") are used as denture bases, artificial teeth, filling materials, and prosthetic materials. However, since the conventional resin is crude and has a high water absorbability, when it is used as a dental treatment material, bacteria may grow in the mouth and cause bad breath. In addition, when the conventional resin is used for the elderly and the weak, there is a harmful effect that a bacterium that does not usually reproduce much is generated around the area where the resin is used and pneumonia or the like is induced. Further, the conventional resin also has a bad effect that plaque is liable to adhere. Therefore, there is a strong demand for a resin having an antibacterial action to prevent the attachment of bacteria.

[0003]

In order to solve the above-mentioned problems, according to the present invention,

Embedded image A benzylammonium derivative represented by
Also, according to the present invention,

Embedded image A benzylammonium derivative represented by
There is also provided a dental treatment material formed by adding 0.001 to 10 weight percent of the benzylammonium derivative shown in Chemical formula 3 or Chemical formula 4 to a room temperature polymerization resin, a filling resin or an adhesive resin. Furthermore, a dental additive comprising the compound shown in Chemical formula 3 or Chemical formula 4 is provided. Preferably, in the benzylammonium derivative shown in Chemical formula 3 or Chemical formula 4, the halogen atom is Cl. Further, preferably, in the benzylammonium derivative shown in Chemical formula 3 or Chemical formula 4, the number of methylene side chains is 10 to 1
4. Further, preferably, in the benzylammonium derivative shown in Chemical formula 3 or Chemical formula 4, the number n of methylene side chains is 11 to 13.

[0004]

BEST MODE FOR CARRYING OUT THE INVENTION The compound of the present invention can be used by adding it to a dental treatment material (resin) used as a denture base, an artificial tooth, a filling material, or a prosthesis material. Next, a method for producing the compound shown in Chemical formula 3 or 4 will be described with reference to Chemical formula 5 shown below.

[0005]

Embedded image

First, the dicarboxylic acid represented by (1) in Chemical formula 5 is heated under reflux to obtain the dicarboxylic acid diester represented by (2). The dicarboxylic acid diester thus obtained is saponified, a solvent such as a hexane-diethyl ether mixed solution is added thereto, and the deposited precipitate is collected by filtration. Water is added to the precipitate, an acid such as 2N-hydrochloric acid is added under ice cooling, and this aqueous solution is extracted with a solvent such as diethyl ether. The diethyl ether layer is washed with saturated saline and the like, and then the solvent is distilled off to obtain the compound shown in (3).

Hexamethylenephosphoramide is added to the compound shown in (3) and heated. After the reaction, the internal temperature is reduced and hexamethylenephosphoramide is distilled off under reduced pressure. A saturated aqueous barium carbonate solution is added to the residue, and the mixture is extracted with an organic solvent such as benzene. Then, after washing the organic layer with water,
dry. The solvent is distilled off to obtain the compound shown in (4). An ether solution of this compound is added dropwise to a solution of a reducing agent such as lithium aluminum hydride (LiAlH ₄ ).
After dropping, reflux. After the reaction, it is treated with a base such as an aqueous sodium hydroxide solution under ice cooling. After the precipitate is filtered off, the solvent is removed to obtain N, N-dimethylamino alcohol shown in (5).

Then, the compound (5) and the benzyl halide are heated, and the solidified crude product is recrystallized from ethanol to obtain the compound (6). The compound represented by (6) is the compound represented by Chemical formula 4.
Thereafter, methacroyl chloride is added to the benzene solution of the compound shown in (6) and the mixture is refluxed. After the reaction, the solvent was distilled off, and the residue was separated by silica gel column chromatography or the like to give compound (7) (n)
= 10-12, methacryloxybenzalkonium chloride (MBKC) is obtained).

As described above, examples of the benzyl halide used to obtain the substance shown in (6) include benzyl chloride, benzyl bromide, benzyl iodide, etc. It is benzyl chloride.

The compounds represented by Chemical formulas 3 and 4 are useful as dental additives. When the compound represented by Chemical formula 3 or Chemical formula 4 is used, for example, a room temperature polymerized resin (for example, trade name "UNIFAST" sold by GC Company), a filling resin (composite resin), or an adhesive resin The compound represented by Chemical formula 3 or Chemical formula 4 is added in an amount of about 0.001 to about 10 weight percent, preferably about 0.1 to about 1 weight percent. It is used as a dental treatment material (that is, a resin) such as a tooth, a filling material, and a prosthesis material.

[0011]

EXAMPLES Among the compounds shown in Chemical formulas 3 and 4, when the halogen atom X is Cl and the number of methylene side chains is 12, the production method is as follows. First, in a 500 ml flask, 46 g of dodecanedicarboxylic acid, 280 ml of ethyl alcohol, and 1 g of p-toluenesulfonic acid were placed, and 15
Heating at reflux at 0 ° C for 5 hours gives dodecadicarboxylic acid diester. To the dodecadicarboxylic acid diester thus obtained, 200 ml of an ethyl alcohol solution containing 12 g of potassium hydroxide was added for saponification, and 300 ml of a hexane-diethyl ether (1: 1) mixed solution was added to this to precipitate the deposited precipitate. Collect by filtration. 100 ml of water was added to the precipitate, and 2N-hydrochloric acid was added under ice cooling to adjust to PH2. This aqueous solution was extracted with 150 ml of diethyl ether. The diethyl ether layer was washed 3 times with 50 ml of saturated saline and the solvent was distilled off to obtain 33.5 g of 11- (ethoxycarbonyl) undecanoic acid.

16.4 g of 11- (ethoxycarbonyl) undecanoic acid and 33 ml of hexamethylenephosphoramide
And heat at 200 ° C. for 4 hours. After the reaction, the internal temperature is reduced to 60 ° C, and hexamethylenephosphoramide is distilled off under reduced pressure. 50 aqueous saturated barium carbonate solution
Add 3 ml and extract 3 times with 50 ml of benzene. Next, the benzene layer is washed 3 times with water and then dried. Benzene was distilled off to obtain 16 g of 11- (N, N-dimethyl) ethoxycarbonylundecanoic acid amide.

A solution of 3 g of 11- (N, N-dimethyl) ethoxycarbonylundecanoic acid amide in 30 ml of ether was added to 0.9 g of lithium aluminum hydride (LiAlH ₄ ).
To 100 ml of ether solution. After dropping, reflux for 2 hours. After the reaction, the mixture is treated with 10% aqueous sodium hydroxide solution under ice cooling. After filtering off the precipitate, the solvent was removed and
1.9 g of-(N, N-dimethylamino) dodecan-1-ol are obtained.

Then, 1.15 g of 12- (N, N-dimethylamino) dodecane-1-ol and 1.15 g of benzyl halide were heated at 100 ° C. for 2 hours, and the solidified crude product was recrystallized from ethanol. Thus, 2 g of the compound shown in Chemical formula 4 (X = Cl, n = 12) is obtained. After that,
Compound (X = Cl, n = 12) 355 mg of 50
Add 500 mg of metacloyl chloride to the ml benzene solution and reflux for 5 hours. After the reaction, the solvent is distilled off, and the residue is separated by silica gel column chromatography (ethyl acetate: methyl alcohol = 1: 1) to obtain the compound shown in Chemical formula 3 (X = Cl, n = 12).

Compound shown in Chemical formula 3 (X = Cl, n = 12)
Is a colorless viscous oily substance, and its elemental analysis value is C7.
0.93, H9.92, N3.45, molecular formula C ₂₅
The theoretical values for H ₄₂ NO ₂ Cl are C70.81, H9.9.
8, N3.30. In addition, ¹ H-NMR (ppm)
Is 1.2 to 1.9 (m, 20H), 1.3 (s, 3
H), 3.3 (s, 6H), 3.5 (m, 2H), 4.
1 (t, 2H), 5.0 (s, 2H), 5.6 (s, 1
H), 6.1 (s, 1H), 7.4 to 7.7 (m, 5)
H) and IR (cm ^-1 ) is 1720.

Experiment 1 An experiment was conducted to measure the minimum inhibitory concentration of the compound shown in Chemical formula 3 (X = Cl, n = 12). First, prepare 16 small test tubes containing 5 ml of liquid medium (BHI),
Each of these small test tubes is divided into 4 groups, and 0.01%, 0.005%, 0.0025%,
The above compounds, each diluted to 0.00125%, were added. Then, in a small test tube of each compound concentration, 4 kinds of bacteria,
That is, Streptococcus mutans
occus mutans), Streptococcus sanguis (Stre
ptococcus sanguis), Actinomyces viscosus, Candida albicans bacterial solution (concentration 1 × 10 ⁸ CF
0.1 ml of U / ml) was injected. After culturing for 24 hours, it was observed with the naked eye, and the one showing no growth of bacteria was defined as the minimum inhibitory concentration.

As a result, the minimum growth rate was 0.01% for Streptococcus mutans, 0.005% for Streptococcus sanguis, 0.01% for Actinomyces viscosus, and 0.01% for Candida albicans. Met.

Experiment 2 0.5 weight percent of the compound (X = Cl, n = 12) shown in Chemical formula 3 was blended with "UNIFAST" sold by GC, and the mixture was polymerized at a standard powder-liquid ratio. Was examined for antibacterial properties. At the time of experiment, first, diameter 13mm, thickness 1m
m, inner diameter 11 mm, and height 8 mm were prepared using Unifast containing 0.5% of the compound. Then, a bacterial solution adjusted to 7 × 10 ⁶ CFU / ml with a broth culture solution was inoculated therein, and aerobically cultured at 37 ° C. for 24 hours. Then, the bacterial solution is recovered and appropriately diluted (10 ^-1 to 1
0 ^-8 ) and then 0.1 on liquid medium (BHI) agar plate.
ml was inoculated and aerobically cultivated at 37 ° C. for 24 hours to observe the degree of growth or reduction of the bacteria, thereby determining the antibacterial effect at the contacted site. Bacteria have a concentration of 7.1 x 1
Candida albicans at 0 ⁶ CFU / ml was used. In order to verify the effect of the compound shown in Chemical formula 3,
Six 0.5% compound-containing samples and three compound-free samples were observed.

As a result, the number of bacteria in the compound-free sample was
5.0 × 10 ⁷ CFU / ml, 4.0 × 10 ⁷ CFU / ml
ml, 2.0 × 10 ⁷ CFU / ml (The above average is
3.66 × 10 ⁷ CFU / ml),
The number of bacteria in the sample containing 0.5% compound was 1.51 × 10 ⁵ C
FU / ml, 1.40 × 10 ⁵ CFU / ml, 2.00
× 10 ⁵ CFU / ml, 1.41 × 10 ⁵ CFU / m
1, 1.10 × 10 ⁵ CFU / ml, 1.00 × 10 ⁵
CFU / ml (The above average is 1.35 × 10 ⁵ CFU
/ Ml). That is, in the compound-free sample,
On the contrary, in the sample containing 0.5% compound, the number of bacteria increased by 5.1 times, on the contrary, the number of bacteria decreased by 1/52 times, demonstrating the effect of the compound shown in Chemical formula 3.

Experiment 3 An experiment was conducted to confirm the durability of the antibacterial effect of the compound shown in Chemical formula 3 (X = Cl, n = 12). First, after collecting the sample used in Experiment 2, ultrasonic cleaning was performed for 20 minutes, and the sample was immersed in water for 12 hours. Then, after sterilizing with ethylene oxide gas, the same procedure as in Experiment 2 was repeated.

As a result, the number of bacteria in the compound-free sample was
1.42 x 10 ⁷ CFU / ml, 2.00 x 10 ⁷ CF
U / ml and 1.00 × 10 ⁷ CFU / ml (the above average is 1.47 × 10 ⁷ CFU / ml), whereas the 0.5% compound-containing sample had a bacterial count of 1 .40 × 10
⁵ CFU / ml, 1.50 × 10 ⁵ CFU / ml, 2.
00 × 10 ⁵ CFU / ml, 1.44 × 10 ⁵ CFU / ml
ml, 1.30 × 10 ⁵ CFU / ml, 5.00 × 10
⁵ CFU / ml (The above average is 2.10 × 10 ⁵ CF
U / ml). That is, in the compound-free sample, the number of bacteria was increased by 11.7 times, while the number was 0.5%.
In the compound-containing sample, the number of bacteria decreased 1/70 times,
It was demonstrated that the compound shown in 1 has a remarkably long-lasting antibacterial effect.

[0022]

The main effect of the compound of the present invention is that it has an antibacterial action to prevent the attachment and growth of bacteria. The secondary effect of the compound of the present invention is to have an adhesive effect, that is, a silane coupling effect. The resin is rarely used alone, and is often used as a mixture of metal, glass particles and the like. Conventional resins do not have an adhesive action with metals and the like and cause troubles during use, but the compound of the present invention can provide a strong bond. Further, as a third effect, the compound of the present invention has permeability and adhesiveness to tooth dentin. Therefore, when the compound of the present invention is added to a dental material used as a material for an artificial tooth or the like, the antibacterial property of the artificial tooth or the like is improved and the adhesion of the tooth to dentin is improved.

Claims (7)

[Claims] (1) Formula (1) And a benzylammonium derivative. 2. The formula: And a benzylammonium derivative. 3. The benzylammonium derivative according to claim 1, wherein the halogen atom X is Cl. 4. The benzylammonium derivative according to claim 1, wherein the number of methylene side chains is 10 to 14. 5. The benzylammonium derivative according to claim 1, wherein the number of methylene side chains is 11 to 13. 6. Dental formed by adding 0.001 to 10% by weight of the benzylammonium derivative according to any one of claims 1 to 5 to a room temperature polymerization resin, a filling resin or an adhesive resin. Treatment material. 7. A dental additive comprising the benzylammonium derivative according to any one of claims 1 to 5.