JPH069725A - Antifungal polymerizable composition and polymer and article obtained therefrom - Google Patents

Abstract

PURPOSE:To obtain a polymer having improved antifungal properties and resistance to the leaching of the antifungal component therefrom by polymerizing an ethylenically unsaturated monomer with a specified mono- to tri-functional antifungal monomer. CONSTITUTION:An ethylenically unsaturated monomer is copolymerized with 0.01-50 wt. % monomer selected from among antifungal mono- to tri-functional compounds of formulas I-III (wherein R1 is H or CH3; R2 is 2-18C alkylene; R3 is H or 1-18C alkyl; R4 is CH3, CH2CH3 or CH2CH2OH; X is O, S or NH; Z is Cl or Br; Y is a group of formula IV or the like; Y' is a group of formula V or the like; and Y'' is a group of formula VI or the like) in the presence of a polymerization initiator.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a polymerizable composition capable of producing an insoluble antibacterial polymer, and more specifically, a polymerizable composition capable of producing a non-eluting antibacterial polymer in which an antibacterial component is not eluted. , And polymers and medical supplies obtained therefrom. The medical products manufactured by the present invention include dental materials (adhesives, coatings, composite resins, etc.), artificial blood vessels, artificial skin, wound dressings, catheters, sutures, contact lenses, bone cements, and the like.

[0002]

2. Description of the Related Art Polymers having antibacterial properties have been known, and one example thereof is a polymer containing an eluent antibacterial component. In order to exhibit antibacterial properties, it is considered necessary for the antibacterial component to be incorporated into bacteria or the like, or to incorporate and kill or inactivate the bacteria, which is why the antibacterial component elutes and is free to interact with the bacteria. It was considered necessary to make contact. For example, the Agency of Industrial Science and Technology R & D materials "Metal / Inorganic / Polymer Materials" Vol. 9 934-939 tribute Synt
hesis and AntibacterialAc
lives of Co-polymers Ha
ving a Quaternary Salt Gr
In the up, the AN copolymer containing a quaternary ammonium chloride group was dissolved and the Bacillus subti
Llis and Staphylococcus aureu
It has antibacterial properties against s. Also JP-A62-2
01806 discloses a dental antibacterial composition containing a known cetylpyridinium salt of a chaotic surfactant.

However, when the antibacterial component is eluted, the antibacterial property decreases with time, and when the antibacterial component is eliminated, the antibacterial property is lost. In addition, the antibacterial component often gives a harmful effect to normal tissue, and the eluted antibacterial component also migrates to a normal tissue, so that the harmful effect cannot be eliminated. Further, there is a problem that the mechanical properties of the material are deteriorated by blending the antibacterial agent.

The problem of antibacterial property in the field of dental materials will be described below. Caries, which is a typical tooth disease,
It develops when the enamel is dissolved by the acid produced by the microorganisms in the oral cavity. Among them, Streptococcus mutans
Is listed as an important causative agent of caries. Also,
Periodontitis, which is a disease of periodontal tissues, is also believed to be caused by oral bacteria. To prevent any disease,
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, and for this reason, it is recommended to brush teeth.

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 of a defective portion (for example, a denture), dental 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 substance with an acidic fluorophosphoric acid solution or a silver fluoride diamine solution is generally performed. There is. Further, as a method for preventing the formation of plaque, particularly plaque on the surface of dental materials, some attempts have been made from the standpoint of materials. As one of the trials, it has been attempted to blend an antibacterial agent into a dental material, and a composite resin blended with chlorohexidine (Takemura Kinzo et al., Journal of Japan Dental Conservation Society, Vol. 26, No. 2, 540-5).
47, 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 in this manner causes the antibacterial agent to be eluted in a short period of time, which is not satisfactory in terms of sustaining the antibacterial effect. In addition, there is a problem that the mechanical properties of the material are deteriorated by blending the antibacterial agent. Further, the elution of the antibacterial agent from the dental composition is concerned not only on the surface of the dental composition but also on the surrounding oral flora.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have completed the present invention by researching to solve the above problems and to produce a polymer in which an antibacterial component does not elute.

[0009]

That is, the present invention provides at least one monomer selected from an ethylenically unsaturated monomer, a monofunctional or trifunctional compound having antibacterial properties represented by the following general formulas i to iii, and Provided is a polymerizable composition containing a polymerization initiator. Also provided is an antibacterial linear copolymer obtained by polymerizing a monofunctional ethylenically unsaturated monomer and a monofunctional antibacterial monomer represented by the following general formula i in the presence of a polymerization initiator. Also,
Also provided is an antibacterial crosslinked polymer obtained by polymerizing a monofunctional or polyfunctional ethylenically unsaturated monomer and an antibacterial monomer represented by the following general formulas i to iii in the presence of a polymerization initiator. Further, the present invention provides an insoluble antibacterial medical product obtained by molding the linear polymer and an insoluble antibacterial medical product obtained by molding the crosslinked polymer.

The polymer obtained from the composition of the present invention has an antibacterial active part, but the antibacterial part does not dissociate and elute from the polymer. The conventional idea cannot explain the reason why the structure of the present polymer exhibits antibacterial properties, but it is considered that the antibacterial part exerts some action on bacteria contacting with the polymer to kill or inactivate the bacteria.

[0011]

[Chemical 2]

Specific examples of antibacterial monomers include the following. As the compound of (i),

[Chemical 3]

[Chemical 4]

As the compound (ii),

[Chemical 5]

As the compound (iii),

[Chemical 6]

The antibacterial monomer is contained in the composition in an amount of 0.01 to
50% by weight is preferably added. If it is 0.01% by weight or less, the antibacterial effect is insufficient, and if it is 50% by weight or more, the physical properties of the polymer (cured product) are deteriorated, which is not preferable.

The composition of the present invention is for producing a desired polymer, and can be supplied to a user in a polymerizable composition for an application in which the user wants to polymerize at the time of use.
It can be supplied as a polymer for use in the form of a polymer. A linear polymer obtained by polymerizing a monofunctional monomer is desirable for applications requiring thermoplasticity and easy moldability. hardness,
At least 1 for applications that require heat resistance, strength, etc.
Cross-linked polymers prepared by polymerizing a monomer mixture containing some multifunctional monomers are desirable. The type and amount of the polyfunctional monomer may be selected according to the purpose.

The polymers obtained according to the invention have antibacterial properties and are therefore preferably used in medical products.
Needless to say, it can be used for daily products and industrial products that require antibacterial properties other than medical applications. The molded article obtained in the present invention is a coating film, film or molded article produced by coating or pouring the composition into a mold and polymerizing the composition. Further, it includes a film, a coating film, a fiber, a hollow fiber (body), and a molded product which are obtained by molding a linear polymer or a partially crosslinked polymer by a well-known molding method.

Specific applications will be described below. For dentistry, it can be used as a composite resin, an adhesive, a fissure filling material, a denture, a resin for a denture base, a coating material, a temporary restoration resin, a resin cement, an artificial dental root, and the like. Since the surface of the dental material is always exposed to the oral cavity, bacteria resident in the oral cavity often propagate. Therefore, it is one of the most effective applications of the present invention. Bone cement, artificial bones, artificial joints and the like can be mentioned as orthopedic applications, but it is more preferable to use as artificial bones as a coating material for the bone surface. Surgical applications include sutures, artificial blood vessels, wound dressings, artificial skin and the like. For ophthalmology, it is preferably used for soft contact lenses and hard contact lenses, but it is more effective for soft contact lenses having a particularly high water content because bacterial growth is often observed in the lenses. In addition, it is also used for medical disposable tubes, catheters and the like. 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.

Examples of the polymerizable monomer used in the present invention include α-cyanoacrylic acid, (meth) acrylic acid, urethane (meth) acrylic acid, crotonic acid, cinnamic acid, sorbic acid, maleic acid and itaconic acid. Esters with monohydric 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-vinylpyrrolidone Examples of mono-N-vinyl compounds, styrene derivatives and the like include monofunctional compounds such as the following,
Polyfunctional (meth) acrylic acid esters and urethane (meth) acrylic acid esters are preferred. In the present invention, (meth) acrylic acid represents acrylic acid and methacrylic acid.

(I) Monofunctional monomer Methyl (meth) acrylate, n- or i-propyl (meth) acrylate, n-, i- or t-butyl (meth) acrylate, 2-hydroxyethyl (meth ) Acrylate, siloxanyl (meth) acrylate and the like.

(Ii) Bifunctional monomer

[Chemical 7] (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 8] (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) Monofunctional or Higher Monomers 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 9] (Here, R ¹ is hydrogen or a methyl group, R ² is an alkylene group, and R ³ is an organic residue.)

As the polymerizable monomer, a compound having an acidic group such as a phosphoric acid group or a carboxyl group can also be used. Examples of these are shown below. (I) containing a phosphate group

[Chemical 10] (R ¹ and R ² are hydrogen or a methyl group, and R ³ and R ⁴ are organic residues.)

[Chemical 11] (R ¹ is hydrogen or a methyl group, R ² is hydrogen or a phenyl group,
n is an integer of 2-14. )

(Ii) having a hydroxyl group as a side chain (meth)
Reaction product of acrylic acid ester and phosphoric acid chloride. For example, there is one as shown in the following formula.

[Chemical 12]

(Iii) having a carboxyl group

[Chemical 13] And its anhydride

[Chemical 14] (R ¹ is hydrogen or a methyl group, R ² is an organic residue.) For example, 4-methacryloyloxyethyl trimellitate anhydride is available.

[0028]

[Chemical 15] (R ¹ is hydrogen or a methyl group, R ² is an organic residue.) For example

[Chemical 16]

As the filler (filler) optionally added in the present invention, quartz powder, alumina powder,
It is possible to use hydroxyapatite, calcium carbonate, fluoroaluminosilicate glass, barium sulfate, titanium oxide, zirconia powder, glass powder, ultrafine particle silica, an organic composite filler containing an organic component and an inorganic component, and the like. Further, polymer powder such as polymethylmethacrylate, polystyrene, polyvinyl chloride and the like are added as needed. Such glass, silica glass, soda lime silicate glass, borosilicate glass,
Examples thereof include barium boroaluminosilicate glass, alumina silicate glass, strontium boroaluminosilicate glass, 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.

[0033]

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

Example 1 17 parts by weight of a mixture comprising 70 parts by weight of BisGMA, 30 parts by weight of triethylene glycol dimethacrylate, 2 parts by weight of compound 1 shown below as an antibacterial component, 1 part by weight of camphorquinone, and 2 parts by weight of dimethylaminoethyl methacrylate. Part and quartz powder surface-treated with γ-methacryloxypropyltrimethoxysilane (average particle size 2.4 μm) 8
3 parts by weight were mixed to manufacture a dental composite resin as a prototype (composition I). A disc-shaped test piece having a diameter of 10 mm and a thickness of 2 mm was polymerized using the composition, and sterilized with ethylene oxide gas, and then the evaluation methods A, A ′, B, and B ′ were used.
The antibacterial property was evaluated in accordance with. The results are shown in Table 1. (Compound 1)

[Chemical 17]

(Evaluation of Antibacterial Property) Evaluation Method A: Streptococcus mutans MT81 cultivated overnight on a prepared BHI (brain heart infusion) agar plate.
48 strain) culture liquid was applied and dried. A test piece from which ethylene oxide gas has been sufficiently removed is placed thereon, and the temperature is set to 37 ° C.
After culturing for 48 hours, the growth condition of the bacteria on the surface of the test piece and the surroundings was observed, and the judgment was made according to the following criteria.

A) Suppression of bacterial growth on the surface of the test piece: No growth inhibition is observed on the agar plate directly below the test piece. Bacteria are growing uniformly on the plate. ±: A slight growth inhibitory effect on the agar plate is observed on the agar plate directly below the test piece. +: Almost no growth of bacteria was observed on the agar plate directly below the test piece. ++: No growth of bacteria is observed on the agar plate directly below the test piece.

(B) Development of developmental inhibition spots: No bacterial growth inhibition spots are observed around the test piece. ±: A ring-shaped stunting patch with a width of less than 1 mm is recognized around the test piece. +: A ring-shaped growth inhibition spot having a width of 1 mm or more and 2 mm or less is recognized around the test piece. ++: Growth inhibition spots with a width of more than 2 mm are observed around the test piece.

Evaluation method A ': The same evaluation as in evaluation method A was carried out using a test piece immersed in water at 37 ° C for one month.

Evaluation method B: 1 × 1 containing 1% sucrose
0 ⁷ CFU / ml S.I. The test piece was suspended in a mutans bacterial solution and cultured at 37 ° C. for 24 hours, and then the plaque (plaque) adhering to the surface of the test piece was dyed to evaluate the plaque adhesion suppressing effect. The judgment was made according to the following criteria. -: Almost no inhibition of plaque adhesion on the surface of the test piece was observed. No difference was observed in plaque adhesion compared to the control containing no antibacterial component. ±: The plaque adhesion on the surface of the test piece is slightly suppressed. +: Plaque adhesion to the surface of the test piece is considerably suppressed. ++: Almost no plaque is observed on the surface of the test piece.

Evaluation method B ': Evaluation was carried out in the same manner as in evaluation method B using a test piece immersed in water at 37 ° C for one month.

Examples 2 to 6 Instead of the composition I used in Example 1, the same evaluations as in Example 1 were carried out by using the respective compositions obtained by replacing Compound 1 with Compounds 2 to 6 shown below. went. The results are shown in Table 1. Similar results are obtained with compositions containing other polymerizable antimicrobial compounds.

(Compound 2)

[Chemical 18] (Compound 3)

[Chemical 19] (Compound 4)

[Chemical 20] (Compound 5)

[Chemical 21] (Compound 6)

[Chemical formula 22]

Comparative Example 1 The same evaluation as in Example 1 was carried out using a composition obtained by removing Compound 1 from Composition I. The results are shown in Table 1.

Comparative Examples 2 to 5 In Composition I, Compound 1 is shown as Compounds 7 to 10 shown below.
The same evaluations as in Example 1 were performed using the respective compositions replaced with. The results are shown in Table 1.

(Compound 7)

[Chemical formula 23] (Compound 8)

[Chemical formula 24] (Compound 9)

[Chemical 25] (Compound 10)

[Chemical formula 26]

[0046]

[Table 1]

Examples 7 to 11 Test pieces were prepared by using each composition obtained by adding a predetermined amount of Compound 1 as an antibacterial component to five kinds of commercially available dental materials (described in Table 2), and evaluating method A, Antibacterial properties were evaluated according to A ', B, B'. The results are shown in Table 2. Similar results are obtained with compositions containing other polymerizable antimicrobial compounds.

Comparative Examples 6 to 10 Test pieces similar to those in Examples 7 to 11 were prepared by using the compound 7 instead of the compound 1 and evaluated. The results are shown in Table 2.
Shown in.

Comparative Examples 11 to 15 The same evaluations as in Examples 7 to 11 were carried out using the commercially available dental material as it was without adding the antibacterial component. The results are shown in Table 2.
Shown in.

[0050]

[Table 2]

Example 12 2-Hydroxyethyl methacrylate (HEMA) 9
6.7 parts by weight, 3 parts by weight of compound 1 and 0.3 parts by weight of ethylene glycol dimethacrylate were bulk polymerized with an azobis polymerization initiator (V-601),
A soft contact lens was prototyped. This is 10m in diameter
After being molded into a flat plate having a thickness of m and a thickness of 0.1 mm, the antibacterial property was evaluated by the following method.

Evaluation Method C Fungus Pa that occurs relatively frequently in soft contact lenses
The ecylomyces lilacinus was separated and pre-cultured to prepare a spore solution, which was then smeared on a PDA medium (potato, dextrose agar medium) plate with a conradi stick. After placing the sample on a PDA plate and culturing at 27 ° C. for 7 days, the growth condition of the bacteria on the surface of the sample and the surroundings was observed, and the judgment was made according to the following criteria.

A) Suppression of bacterial growth on the surface of the sample-: No growth inhibition of the bacterial is observed on the surface of the sample or on the agar plate immediately below the sample. ±: A slight growth inhibitory effect of bacteria is observed on the surface of the sample and on the agar plate directly below the sample. +: Almost no growth of bacteria was observed on the surface of the sample and on the agar plate immediately below the sample.

(B) Expression of growth inhibition spots: No growth inhibition spots of bacteria are observed around the sample. ±: Some growth inhibition spots are observed around the sample. +: A clear stunted spot is observed around the sample.

Evaluation method C ′ Evaluation was carried out in the same manner as in evaluation method C using a sample immersed in water at 37 ° C. for one month. The evaluation results are shown in Table 3.

Examples 13 to 17 Instead of the compound 1 used in Example 12, compounds 2 to 6 were used.
Was used and the same evaluation as in Example 12 was performed. The results are shown in Table 3. Similar results are obtained with compositions containing other polymerizable antimicrobial compounds.

Comparative Example 16 The same evaluation as in Example 12 was carried out using the composition of Example 12 in which the compound 1 was replaced by HEMA. The results are shown in Table 3.

Comparative Examples 17 to 20 The same evaluations as in Example 12 were carried out using the respective compositions obtained by replacing Compound 1 with Compounds 7 to 10 in Example 12.
The results are shown in Table 3.

[0059]

[Table 3]

Example 18 Evaluation method D Pseudomonas aeruginosa, which is commonly found in corneal infections of contact lens wearers, was isolated and precultured, and this bacterial solution was plated on a BHI (Brain Heart Infusion) agar medium plate. It was smeared with a large stick. The same sample as in Example 12 was placed on a BHI plate and aerobically cultured at 37 ° C. for 48 hours, then the growth status of the bacteria on the sample surface and in the surroundings was observed, and evaluation was performed according to the same evaluation criteria as in evaluation method C. . The results are shown in Table 4.

Evaluation method D'Evaluation was carried out in the same manner as in evaluation method D using a sample immersed in 37 ° C. water for one month. The results are shown in Table 4.

Example 19 The P. aeruginosa instead of Staphylococcus epi
The same evaluation as in Example 18 (evaluation methods D and D ′) was performed using Dermidis. The results are shown in Table 4.

Example 20 The P. Instead of aeruginosa, Streptococcus pyogenes
The same evaluation as in Example 18 was performed using “nes”. The results are shown in Table 4.

Comparative Examples 21, 22, and 23 Examples 18 and 1 were prepared by using a sample in which the compound 1 was replaced by HEMA in the components of the sample used in Example 18 (Example 12).
The same evaluations as 9 and 20 were performed. The results are shown in Table 4.

Comparative Examples 24, 25 and 26 Examples 18 and 1 were prepared by using a sample in which the compound 1 was replaced by the compound 7 in the components of the sample used in the example 18 (example 12).
The same evaluations as 9 and 20 were performed. The results are shown in Table 4.

[0066]

[Table 4]

Examples 21, 22, and 23 A composition containing 67 parts by weight of methyl methacrylate (MMA), 30 parts by weight of siloxanyl methacrylate, and 3 parts by weight of compound 1 was bulked with an azobis polymerization initiator (V-601). Polymerization was carried out to produce a hard contact lens as a prototype. After molding this into a flat plate having a diameter of 10 mm and a thickness of 0.2 mm, the same evaluation as in Examples 18, 19, and 20 (evaluation methods D and D ′) was performed. The results are shown in Table 5.

Comparative Examples 27, 28, 29 Among the components of the sample used in Example 21, the same evaluation as in Examples 21, 22, 23 was performed using a sample in which the compound 1 was replaced with MMA. The results are shown in Table 5.

Comparative Examples 30, 31, 32 Among the components of the sample used in Example 21, compound 1 was replaced with compound 7
The same evaluations as in Examples 21, 22, and 23 were performed using the sample replaced with. The results are shown in Table 5.

[0070]

[Table 5]

Example 24 A bone cement consisting of the following powder and liquid was manufactured as a trial. The powder agent and the liquid agent were kneaded at a powder-liquid ratio of 2/1 (g / ml), filled in a split mold having a diameter of 10 mm and a thickness of 3 mm and cured. The cured product was stored at 37 ° C. for 1 day and then evaluated in the same manner as in Example 20. The results are shown in Table 6.

Powder agent Polymethylmethacrylate (PMMA) 89 parts by weight Barium sulfate 10 〃 Benzoyl peroxide 1 〃 Liquid agent Methylmethacrylate (MMA) 88 parts by weight Compound 1 10 〃 N, N-diethanol-p-toluidine 2 〃

Examples 25 to 29 The same evaluations as in Example 24 were carried out by using compounds 2, 3, 4, 5 and 6 instead of compound 1. The results are shown in Table 6.

Example 30 A composition comprising 95 parts by weight of MMA and 5 parts by weight of compound 1 was emulsion polymerized to obtain a fine particle polymer (polymer A).
Using this, the following bone cement was prototyped, and Example 2 was used.
The same evaluation as in 4 was performed. The results are shown in Table 6.

Powder agent Polymer A 89 parts by weight Barium sulfate 10 〃 Benzoyl peroxide 1 〃 Liquid agent MMA 98 parts by weight N, N-diethanol-p-toluidine 2 〃

Examples 31, 32, 33 Compounds 2, 4, 5 were used in place of compound 1
The same evaluation as 0 was performed. The results are shown in Table 6.

Comparative Example 33 The same evaluation as in Example 24 was carried out by using bone cement in which the liquid compound 1 was replaced with MMA. The results are shown in Table 6.

Comparative Examples 34 to 37 The same evaluations as in Example 24 were carried out using the bone cements obtained by replacing Compound 1 with Compounds 7 to 10 in Example 24.
The results are shown in Table 6.

[0079]

[Table 6]

Examples 34, 35, 36 5 g of Compound 1 was dissolved in 100 ml of water, and 5 g of a collagen nonwoven fabric was immersed therein. To this, 2.5 ml of a 1N nitric acid solution having a cerium ammonium nitrate concentration of 0.1 mol / l was added, polymerized at 20 ° C. for 10 hours in a nitrogen atmosphere, and then repeatedly washed with water and acetone to give Compound 1 to the collagen nonwoven fabric. A graft-polymerized wound dressing (artificial skin) was prototyped.
This was cut into a sheet of 10 × 10 mm square and used as a sample for evaluation of antibacterial property, and evaluation was performed by the same method as in Examples 18, 19, and 20 (evaluation methods D and D ′). The results are shown in Table 7.
Shown in.

Examples 37 to 41 The same evaluations as in Example 34 were carried out by using compounds 2 to 6 instead of compound 1. The results are shown in Table 7.

Comparative Example 38 The same evaluation as in Example 34 was carried out using a collagen nonwoven fabric. The results are shown in Table 7.

[0083]

[Table 7]

Example 42 A composition comprising 80 parts by weight of MMA and 20 parts by weight of compound 1 was subjected to bulk polymerization with an azobis polymerization initiator (V-601) to obtain a polymer B (number average molecular weight, about 50,000). .
In order to remove the residual monomer, it was dissolved in methylene chloride, reprecipitated with hexane, and filtered to use polymer B. A methylene chloride solution (5 wt%) of the polymer B was prepared, and a catheter (made of polyvinyl chloride) was immersed in the solution and taken out, and methylene chloride was sufficiently evaporated to prepare a catheter in which the polymer B was coated on the surface layer. Using the surface-treated catheter and the untreated catheter, comparative evaluation of antibacterial properties was performed by the following method.

Evaluation method E: Staphylo Staphylo
After coccus epidermidis was separated and pre-cultured, this bacterial solution was inoculated into a BHI medium, and the sample was immersed in the liquid medium and aerobically cultured at 37 ° C. for 48 hours. The sample was taken out and stained with Gram to observe the growth of bacteria on the surface of the sample, and the judgment was made according to the following criteria.

-: No growth inhibition was observed in the surface-treated sample (growth of bacteria equal to or higher than in the untreated sample). ±: A slight growth inhibitory effect is observed in the surface-treated sample (less bacterial growth than in the untreated sample). +: Almost no growth of bacteria was observed in the surface-treated sample. The evaluation results are shown in Table 8.

Examples 43, 44, 45 Instead of the catheter used in Example 42, a suture (made of silk), artificial skin (made of formalized polyvinyl alcohol), and artificial blood vessel (made of segmented polyurethane) were used. The same evaluation as in Example 42 was performed. The results are shown in Table 8.

Comparative Examples 39-42 Using PMMA instead of Polymer B Examples 42-
The same evaluation as in 45 was performed. The results are shown in Table 8.

[0089]

[Table 8]

[0090]

As described above, the cured product and polymer obtained from the composition of the present invention as shown in the examples have the antibacterial property lasting without elution of the antibacterial component in water, and the antibacterial property is only on the surface of the composition. It is an excellent medical composition which is limited to

Continuation of front page (51) Int.Cl. ⁵ Identification number Office reference number FI Technical display location C07D 213/30 215/10 219/02 C08F 220/34 MMQ 7242-4J MMW 7242-4J 220/38 MMU 7242- 4J 220/60 MNH 7242-4J MNJ 7242-4J (72) Inventor Junichi Yamauchi 1621 Sakata, Kurashiki City, Okayama Prefecture Kuraray Co., Ltd.

Claims (5)

[Claims] 1. A polymerizable composition comprising an ethylenically unsaturated monomer, at least one monomer selected from monofunctional or trifunctional compounds having antibacterial properties represented by the following general formulas i to iii, and a polymerization initiator. Composition. 2. An antibacterial linear copolymer obtained by polymerizing a monofunctional ethylenically unsaturated monomer and a monofunctional antibacterial monomer represented by the following general formula i in the presence of a polymerization initiator. 3. An antibacterial crosslinked polymer obtained by polymerizing a monofunctional or polyfunctional ethylenically unsaturated monomer and an antibacterial monomer represented by the following general formulas i to iii in the presence of a polymerization initiator. 4. An insoluble antibacterial medical article obtained by molding the polymer according to claim 2. 5. An insoluble antibacterial medical article obtained by molding the polymer according to claim 3. [Chemical 1]