JP2003055108A - Antimicrobial polymer substance and antimicrobial polymer gel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new antimicrobial polymer substance having hydrophilicity or water absorption properties, and an antimicrobial polymer gel. SOLUTION: The antimicrobial polymer substance is characterized by comprising a copolymer obtained by copolymerizing a monomer represented by formula (1) (R<1> is a 1-18C straight-chain or branched chain-containing alkyl group; R<2> and R<3> are each methyl group; X<-1> is a counter ion) with a copolymerizable monomer. The antimicrobial polymer gel is characterized in that water is added to the antimicrobial polymer substance to exhibit a gel-like state.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antibacterial polymer substance and an antibacterial polymer gel composed of a copolymer having antibacterial properties.

[0002]

2. Description of the Related Art Conventionally, various kinds of antibacterial substances have been known, but an antibacterial polymer gel having a proper hydrophilicity or water absorption property and containing water to form a gel form is formed. It is desired to provide an antibacterial polymer substance that can be produced and is easy to manufacture.

[0003]

The present invention has been made under the circumstances described above, and its object is to provide a novel antibacterial polymer substance having appropriate hydrophilicity or water absorbency. To do. Another object of the present invention is to provide a novel antibacterial polymer gel.

[0004]

The antibacterial polymeric substance of the present invention can be copolymerized with a monomer comprising a quaternary ammonium salt compound represented by the following general formula (1) and the monomer. It is characterized by comprising a copolymer obtained by copolymerizing with another copolymerizable monomer.

[Chemical 2] (In the formula, R ¹ is a linear or side chain alkyl group having 1 to 18 carbon atoms, R ² and R ³ are methyl groups, X
^-Indicates a counter ion. )

In the above, the copolymerizable monomer is preferably a hydrophilic monomer, and the hydrophilic monomer is preferably at least one of acrylamide and methacrylamide. In addition, the copolymer is the above general formula (1)
It is preferable that it is obtained by copolymerizing a monomer composed of a quaternary ammonium salt compound represented by, acrylamide, and a crosslinkable monomer. Here, it is preferable that the copolymer contains a component composed of a monomer composed of the quaternary ammonium salt compound represented by the general formula (1) at a ratio of 1 to 10 mol%.

The antibacterial polymer gel of the present invention is characterized in that the above antibacterial polymer substance contains water to form a gel.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. <Antibacterial polymer substance> The antibacterial polymer substance of the present invention has a polymerizable functional group having an unsaturated double bond in the molecule represented by the above general formula (1) and exhibits antibacterial properties. A monomer comprising a quaternary ammonium salt compound having an exerting atomic group (hereinafter, also simply referred to as "antimicrobial monomer"),
It comprises a copolymer obtained by copolymerizing this antibacterial monomer and a copolymerizable monomer.

In the above general formula (1), the group R ¹ is an alkyl group having 1 to 18 carbon atoms, particularly 9 to 1 carbon atoms.
An alkyl group of 7 is preferred. Specific examples of such an antibacterial monomer include vinylbenzyldimethyl n-octylammonium salt, vinylbenzyldimethyl n-decylammonium salt, vinylbenzyldimethyl n-dodecylammonium salt, vinylbenzyldimethyl n-hexadecylammonium salt. And the like, but it is particularly preferable to use vinylbenzyldimethyl n-hexadecyl ammonium salt. The counter ion is preferably chlorine ion or bromine ion.

And, the component made of the above-mentioned antibacterial monomer is
1 to 10 in a copolymer constituting an antibacterial polymer substance
It is preferably contained at a ratio of mol%, particularly 3 to 8 mol%. When this ratio is less than 1 mol%, sufficient antibacterial action may not be obtained.

The copolymerizable monomer copolymerizable with the antibacterial monomer is not particularly limited, but a hydrophilic monomer is used because a hydrophilic copolymer can be obtained. As such a hydrophilic monomer, for example, acrylamide, methacrylamide, N, N-dimethylacrylamide, N-methylacrylamide, N-methylmethacrylamide, N-vinyl-N-methylacetamide, N-isopropyl. Acrylamide, N- (2-hydroxypropyl) acrylamide, N- (2-hydroxypropyl) methacrylamide, N, N-dimethyl methacrylate, 2-hydroxyethyl acrylate,
2-hydroxyethyl methacrylate, hydroxypropyl methacrylate, 4-hydroxybutyl methacrylate, N-acryloyl tris (hydroxymethyl) methylamine, N-methacryloyl tris (hydroxymethyl) methylamine, vinylpyrrolidone, N-acryloylmorpholine and the like can be used. It is possible, and it is particularly preferable to use acrylamide. These hydrophilic monomers may be used alone or in combination of two or more.

In the present invention, a crosslinkable monomer having a plurality of unsaturated double bonds can be used as a part of the copolymerizable monomer. The crosslinkable monomer is not particularly limited, but for example, N, N'-methylenebisacrylamide, N, N'-methylenebismethacrylamide, diethylene glycol diacrylate, diethylene glycol dimethacrylate, diethylene glycol divinyl ether, Ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylate,
It is preferable to use poly (ethylene glycol) dimethacrylate, poly (propylene glycol) dimethacrylate, and the like, and it is particularly preferable to use N, N′-methylenebisacrylamide. The crosslinkable monomers may be used alone or in combination of two or more.

The crosslinkable monomer is preferably contained in a proportion of, for example, 0.1 to 5.0 mol% of all the monomers. By containing the crosslinkable monomer, the obtained copolymer forms a three-dimensional network structure, whereby elution of the antibacterial component is suppressed and excellent durability can be obtained.

<Polymerization Method> The method for obtaining the above copolymer is not particularly limited, and a generally used polymerization method can be used. Specifically, a radical polymerization initiator is used. The radical polymerization reaction described above can be preferably utilized. The radical polymerization initiator can be used without particular limitation as long as it is a commonly used radical polymerization initiator, and for example, hydrogen peroxide, ammonium persulfate, potassium persulfate, t-butyl hydroperoxide, Azobisisobutyronitrile, 2,2 '
-Azobis (2-methylpropionamide) dihydroxy chloride, 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydroxy chloride, 2,2'-azobis (2-amidinopropane) dihydroxy chloride, etc. Can be mentioned. Also,
Known redox type initiators such as hydrogen peroxide and ferrous sulfate, potassium persulfate and sodium bisulfite, and the like can also be used.

As the solvent used in the polymerization reaction, water, a mixed liquid of water and a water-soluble organic solvent, or the like can be used. Specific examples of the water-soluble organic solvent include methanol, ethanol, isopropanol, and n.
There may be mentioned alcohols such as propanol, amide compounds such as formamide and dimethylformamide, and polar solvents such as dioxane, acetonitrile and dimethylsulfoxide. The polymerization reaction may be carried out at a temperature and a reaction time depending on the types of monomers and radical polymerization initiators used and other conditions. For example, the polymerization reaction temperature is 50 to 90 ° C. and the polymerization reaction time is 3 to 24 hours. It is considered as a degree. In this polymerization reaction, it is usually necessary to establish an inert gas atmosphere such as nitrogen gas.

The antibacterial macromolecular substance composed of the above-mentioned copolymer has, for example, a repeating unit represented by the following general formula (2). According to this copolymer, the antibacterial component of the antibacterial monomer is used. By containing, the antibacterial action is obtained, and since the antibacterial component constitutes a part of the molecular structure of the polymer, it does not elute outside. Further, by selecting the type of copolymerizable monomer, it is possible to obtain specific characteristics in the obtained copolymer, for example, by using a copolymerizable monomer having a hydrophilic group, an appropriate An antibacterial polymer substance having hydrophilicity or water absorption can be obtained.

[0016]

[Chemical 3]

<Antibacterial Polymer Gel> The antibacterial polymer substance obtained as described above has appropriate hydrophilicity or water absorbability, and therefore, for example, is made into a powdered antibacterial polymer substance. By contacting with water and swelling, an antibacterial polymer gel, which is a jam-like high-viscosity fluid having an appropriate viscosity, can be obtained. The viscosity of this antibacterial polymer gel has a deviation rate of 6.8 to 1 at room temperature.
The viscosity at the time of 7 sec ^-1 is 8.0~30.0Nsm ^-2,
It is particularly preferably 8.5 to 24.0 Nsm ⁻² .

According to the antibacterial polymer gel of the present invention, the antibacterial action is obtained by containing the antibacterial component by the antibacterial monomer, and the antibacterial component is contained even though it contains water. Does not elute, and therefore, it can be suitably applied to various uses by utilizing its gel form, and its antibacterial property or antibacterial action is stably exhibited for a long period of time.

The above-mentioned antibacterial macromolecular substance can be used for various purposes as an antibacterial material having hydrophilicity or water absorbency, and is applied to human bodies and animals such as diapers, sanitary products and blood absorbents. Sanitary or medical products, surface treatment of tools and equipment for processing or storage of kitchen and various foods, treatment and processing of gardening and construction materials such as civil engineering sealing materials, and other items requiring antibacterial action , Can be applied to any place. Further, for example, an antibacterial film can be formed by mixing with a polymer having various film forming properties, and the antibacterial film can be suitably used as a packaging material, a surface protective material, or the like.

The antibacterial polymer gel is useful, for example, as a filling material for filling voids and the like by utilizing its gel state. It is possible to obtain a water retention effect or a moisturization effect on an object. Then, in particular, an antibacterial polymer gel having an appropriate viscosity, for example, a core-shaped sample (hereinafter, simply referred to as “crustal core sample”) collected from the underwater crust for the purpose of microbial research, and the like. Can be used as a surface protective material of the sample, in which case it is transported and stored in the form of a powdery antibacterial polymeric substance having a significantly small weight, and swelled with water at the sample collection site to antibacterial properties. It is preferable to facilitate the handling of the polymer gel by preparing it.

Although the antibacterial polymer substance and the antibacterial polymer gel of the present invention have been described above, various modifications can be made in the present invention.

[0022]

[Experimental example] <Preparation example 1> (Preparation of antibacterial monomer) In a four-necked flask having a capacity of 100 ml equipped with a dropping funnel, a stirrer and a temperature sensor, 7.63 g (0.05 mo) of chloromethylstyrene was added.
l) and 50 ml of n-hexane are added and this is added to 25
Dimethyl n-hexadecylamine 1 while stirring at ℃
6.17 g (0.06 mol) was added dropwise from the dropping funnel over 30 minutes. The resulting solution was stirred at 25 ° C. for 8 hours, then the precipitate was collected by filtration, washed with n-hexane and diethyl ether, and then dried to obtain a white solid unsaturated double bond. Vinylbenzyldimethyl n which is a quaternary ammonium salt compound having a bond
-Hexadecyl ammonium chloride was obtained.

(Copolymerization reaction) 23.6 g (665 mM) of acrylamide which is a copolymerizable monomer, and N, N '
-Methylenebisacrylamide 0.65 g (8.4 m
M) and 2,2'-azobis (2-amidinopropane)
0.24 g (1.8 mM) of dihydrochloride and vinylbenzyldimethyl n-hexadecyl ammonium chloride, which is the antibacterial monomer obtained in Preparation Example 1 above.
4g (35mM) and 500g of pure water as a polymerization reaction solvent
It was added together with ml to a pressure bottle as a reactor, and the internal air was replaced with nitrogen gas for 30 minutes, and then the pressure bottle holding the polymerization reaction solution was placed in an incubator at 70 ° C. to carry out a polymerization reaction treatment. Remove the obtained polymer from the pressure bottle,
Sample 1 was obtained by immersing in distilled water to remove unreacted residual monomer, and pulverizing the obtained solid copolymer.

<Preparation Examples 2 to 5> In the preparation of the antibacterial monomer in Preparation Example 1, the antibacterial monomer was used in the same manner except that various amine compounds were used in place of dimethyl n-hexadecylamine. Got the body That is, in Preparation Example 2, vinyl benzyl dimethyl n-octyl ammonium chloride, which is an antibacterial monomer, was prepared using dimethyl n-octyl amine, and in Preparation Example 3, dimethyl n-decyl amine was used to prepare vinyl benzyl dimethyl n. -Decyl ammonium chloride was prepared, in Preparation Example 4 vinylbenzyl dimethyl n-dodecyl ammonium chloride was prepared using dimethyl n-dodecyl amine, and in Preparation Example 5, dimethyl n-tetradecyl amine was used. Benzyl dimethyl n-tetradecyl ammonium chloride was prepared.

Then, a copolymerization reaction was carried out in the same manner as in Preparation Example 1 by using the antibacterial monomer obtained in each of Preparation Examples 2 to 5 above to obtain a copolymer. . These are designated as Sample 2 to Sample 5, respectively.

<Preparation example of comparative reference sample> 24.9 g (700 mM) of acrylamide and 0.65 g (8.4 mM) of N, N'-methylenebisacrylamide;
0.24 g (1.8 mM) of 2'-azobis (2-amidinopropane) dihydrochloride and 500 ml of pure water as a polymerization reaction solvent were added to a pressure bottle as a reactor, and the internal air was replaced with nitrogen gas at 30 After substituting for a minute, the pressure resistant bottle holding the polymerization reaction solution was subjected to a polymerization reaction treatment in an incubator at 70 ° C. The obtained polymer was taken out of the pressure bottle, immersed in distilled water to remove unreacted residual monomer, and the obtained solid copolymer was pulverized to obtain a reference sample for comparison.

<Experimental Example 1> (Evaluation of antibacterial property on gel surface) Each of the microorganisms shown in Table 1 below was obtained by adding and dispersing the microorganisms in a physiological saline solution so that the number of bacteria was 1 × 10 ⁵ cells / ml. Each of the bacterial solutions was spread on an agar plate containing no medium components. However, the bacterium is Streptomyces albus (Str
eptomyces albus IFO 1301
4) and Aspergill Stereus
In the case of lus terreus IFO 6346), it was difficult to prepare a physiological saline solution in which the bacterial cells were uniformly dispersed, so the bacterial cells were inoculated on the agar plate using a toothpick. Then, on the bacterial solution applied to the agar plate, the sample 1 of the above Preparation Example 1 to Preparation Example 5
Each of the antibacterial polymer gel obtained from sample 5 and the reference sample for comparison was overlaid and left at room temperature for 3 hours. In the above experiment, each antibacterial polymer gel contained
The antibacterial monomer is added at a ratio of 5 mol%. The bacteria used are as follows.

[0028]

[Table 1]

Thereafter, the medium components were dropped on each anti-polymer gel and the reference sample for comparison, and at the optimum growth temperature of each bacterial species, 24 hours for Escherichia coli and Pseudomonas aeruginosa, Bacillus subtilis. Culturing was carried out for 48 hours for Aspergillus terreus and for 72 hours for other bacterial species. After culturing, the number of colonies formed per unit area on the agar plate which was brought into contact with each sample or the reference sample for comparison was counted and evaluated. That is, the following formula 1
When the calculated survival rate A is 1% or less, "excellent", when the survival rate A is 1 to 10% or less, "good", the survival rate A is 1
The case of exceeding 0% was evaluated as "impossible", and the results of the evaluation for each of Sample 1 to Sample 5 are shown in Table 2 below. However, in the case where the bacteria are Streptomyces albus and Aspergillus terreus, it is “excellent” when no colonies are apparently formed on the agar plate in contact with the antibacterial polymer gel, and “impossible” in other cases. Was evaluated. Here, the survival rate A is calculated by the following equation 1.

[0030]

[Formula 1] Viability A (%) = (Number of colonies formed per unit area on the agar plate contacted with the antibacterial polymer gel / Per unit area on the agar plate contacted with the reference sample for comparison Number of colonies formed on) x 100

<Experimental Example 2> (Evaluation of antibacterial activity of gel against invasion of foreign foreign microorganisms)
Each of Sample 1 to Sample 5 and the reference sample for comparison was packed in the bottom of a column having an inner diameter of 15 mm to have a thickness of 10 mm. Then, each of the microorganisms shown in Table 1 above was added to a physiological saline solution so that the number of bacteria was 1 × 10 ⁷ cells / ml and dispersed, and 5 ml of each of the obtained bacterial solutions was added to the column and allowed to stand at room temperature. did. Here, in Streptomyces arbus and Aspergillus terreus,
The cultured bacterial cells were added to a physiological saline solution, vigorously stirred, and centrifuged to use a supernatant solution obtained. Then, the physiological saline solution dropped from under the column was collected and applied on the agar medium. Further, since the physiological saline solution did not drop from the reference sample for comparison, the physiological saline solution before passing through the antibacterial polymer gel was applied on the agar medium for comparison. Then, culturing was performed at an optimum growth temperature for each bacterial species, the number of colonies formed was counted, and when the survival rate B calculated by the following equation 2 was 1% or less, "excellent" and the survival rate B were 1 The case of -10% or less was evaluated as "good", and the case of the survival rate B exceeding 10% was evaluated as "impossible", and the results of evaluation of each sample 1 to sample 5 are shown in Table 2 below. However, in the case where the bacteria were Streptomyces albus and Aspergillus terreus, the case where no apparent colony was formed on the agar medium was evaluated as "excellent", and the other cases were evaluated as "impossible". Here, the survival rate B is calculated by the following equation 2.

[0032]

## EQU00002 ## Formula 2 Survival rate B (%) = (number of colonies formed from saline solution passing through antibacterial polymer gel / number of colonies formed from saline solution before passing antibacterial polymer gel) ×
100

<Experimental Example 3> (Evaluation of antibacterial activity of gel using crust core sample) A crust core sample actually obtained by excavating the crust, sample 1
-The one covered with each of the antibacterial polymer gel obtained from Sample 5 and the reference sample for comparison was left for 3 hours at room temperature. Then, each of the antibacterial polymer gel and the coating layer of the reference sample for comparison was infiltrated with a medium from the outside, and cultured at room temperature for 72 hours, and the number of colonies formed on the surface of the crust core sample was measured, The case where the survival rate C calculated by the following formula 3 is 1% or less is “excellent”, and the survival rate C is 1 to
The case of 10% or less was evaluated as "good", and the case of the survival rate C exceeding 10% was evaluated as "impossible", and the results of evaluation of each of Samples 1 to 5 are shown in Table 3 below. Where survival rate C
Is calculated by the following equation 3.

[0034]

Formula 3 Survival rate C (%) = (number of colonies formed per unit area of crust core sample covered with antibacterial polymer gel / per unit area of crust core sample covered with reference sample for comparison) Number of colonies formed on) x 100

[0035]

[Table 2]

In Table 2 above, column A is a column showing the evaluation of antibacterial properties on the gel surface, and column B is a column showing the evaluation of antibacterial properties of the gel against invasion of foreign foreign microorganisms.

[0037]

[Table 3]

From the results of Tables 2 and 3 above, Samples 1 to 1
It is clear that the antibacterial polymer gel of Sample 5 exhibits excellent antibacterial properties against various microorganisms.

[0039]

According to the antibacterial polymer substance of the present invention, the antibacterial action is obtained by containing the antibacterial component by the antibacterial monomer, and the antibacterial component has one of the molecular structures of the polymer. Since it constitutes a part, it does not elute outside. Further, according to the antibacterial polymer gel of the present invention,
Since it can be easily obtained by bringing water into contact with the above antibacterial macromolecular substance and swelling it, an antibacterial action by the antibacterial component is obtained, and the antibacterial component is contained even though it contains water. Does not elute, and therefore, it can be suitably applied to various uses by utilizing its gel form, and its antibacterial property or antibacterial action is stably exhibited for a long period of time.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61L 15/00 A61L 15/00 A61P 29/00 A61P 29/00 C08F 212/14 C08F 212/14 220/56 220/56 // A61F 13/15 A61F 13/18 381 13/472 (72) Inventor Kaoru Tsujii 2-15 Natsushima Town, Yokosuka City, Kanagawa Prefecture Marine Science and Technology Center (72) Inventor Hiroki Kogoshi Yokosuka City, Kanagawa Prefecture Natsushima-cho 2-15 marine Science and technology Center in the F-term (reference) 4C003 AA11 BA06 CA04 HA02 4C081 AA01 BA14 4H011 AA02 BA01 BB04 BC19 DA17 DH02 DH06 4J100 AB07P AE76R AL66R AM15Q AM17Q AM19Q AM21Q AM24R AQ08Q BA02R BA03Q BA08R BA32P CA05 CA23 JA00 JA50

Claims (6)

[Claims] 1. Obtained by copolymerizing a monomer comprising a quaternary ammonium salt compound represented by the following general formula (1) and a copolymerizable monomer copolymerizable with this monomer. An antibacterial macromolecular substance, characterized in that it comprises a copolymer. [Chemical 1] (In the formula, R ¹ is a linear or side chain alkyl group having 1 to 18 carbon atoms, R ² and R ³ are methyl groups, X
^-Indicates a counter ion. ) 2. The antibacterial polymer substance according to claim 1, wherein the copolymerizable monomer is a hydrophilic monomer. 3. The antibacterial polymer substance according to claim 2, wherein the hydrophilic monomer is at least one of acrylamide and methacrylamide. 4. A copolymer comprising a monomer comprising the quaternary ammonium salt compound represented by the general formula (1) according to claim 1, acrylamide, and a crosslinkable monomer. The antibacterial polymer substance according to claim 1, which is obtained by 5. The copolymer contains a monomer component consisting of a quaternary ammonium salt compound represented by the general formula (1) according to claim 1 in a proportion of 1 to 10 mol%. The antibacterial polymer substance according to any one of claims 1 to 4, which is a substance. 6. An antibacterial polymer gel, characterized in that the antibacterial polymer substance according to any one of claims 1 to 5 contains water to form a gel.