JPH05117106A - Antibacterial agent consisting of polyelectrolyte complex and antibacterial material - Google Patents

Abstract

(57) [Summary] [Objective] To provide a polyelectrolyte complex antibacterial agent and an antibacterial material. [Structure] The antibacterial agent is a polymer electrolyte prepared by reacting a polymer of a basic amino acid or a quaternary ammonium compound as a cationic polymer with an anionic polysaccharide, an acidic amino acid polymer or an acrylic acid-based polymer as an anionic polymer. It consists of a complex. The antibacterial material supports the polyelectrolyte complex on various carriers. [Effect] Since the antibacterial agent of the present invention is insoluble, it can be used in a wide variety of applications, the antibacterial activity is maintained for a long time, and antibacterial agents having various antibacterial strengths can be easily provided.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antibacterial agent comprising a polymer electrolyte complex and an antibacterial material carrying the polymer electrolyte complex.

[0002]

2. Description of the Related Art It is known that an organic compound having a positive charge exhibits antibacterial properties regardless of whether it is a low molecular weight compound or a high molecular weight compound. Applied technology utilizing this property is widely spread from the medical field to general clothing. For example, the fourth typified by benzalkonium chloride
Since the quaternary ammonium compound is water-soluble, it is itself used as a sterilizing / disinfecting liquid. But, conversely,
Since it is water-soluble, its range of use as an antibacterial agent is limited.

Further, by introducing an anionic group on the surface of a synthetic polymer molded article and subsequently treating it with a quaternary ammonium base, a material exhibiting a long-term antibacterial property is obtained to obtain an air filter or an air filter. It is also used as a filtering material for dialysis. Furthermore, this technique is applied to a textile material and used as a clothing or a wound protector having antibacterial properties.

For example, as a means for introducing a quaternary ammonium into the surface of a polymer material to obtain a material exhibiting a continuous antibacterial property, JP-A-54-86584 discloses that an acidic group-containing monomer is polymerized. A method of contacting the obtained polymeric substance with an aqueous solution of a quaternary ammonium base is described.
Further, JP-A-59-164342 discloses a method in which an anionic group-containing vinyl monomer is introduced onto the surface of a synthetic polymer molded article by graft polymerization or the like, followed by treatment with a quaternary ammonium salt group. There is.

However, in the conventional method, the introduction rate of the quaternary ammonium salt group exhibiting antibacterial properties is not always sufficient, and the durability is not satisfactory.
Furthermore, the manufacturing method was complicated.

[0006]

DISCLOSURE OF THE INVENTION The present inventors have obtained a material having a property of being insoluble in a solvent (particularly water) while maintaining the antibacterial property of a positively charged organic compound and having a persistent antibacterial action. As a result of intensive studies aimed at, it was found that these objects can be achieved by a polyelectrolyte complex obtained by reacting a specific anionic polymer with a specific cationic polymer. The present invention is based on such findings.

[0007]

SUMMARY OF THE INVENTION Therefore, the present invention provides
(1) General formula (I)

[0008]

[Chemical 6]

A cationic polymer represented by the formula [In the general formula (I), R ₁ and R ₄ are preferably each independently a linear or branched alkylene group having 2 to 8 carbon atoms,
R ₁₁ and R ₁₂ are preferably bonded at the p-position], that is, a quaternary ammonium salt polymer or the general formula (II)

[0010]

[Chemical 7]

A cationic polymer represented by the formula: quaternary ammonium salt polymer, (2) general formula (III)

[0012]

[Chemical 8]

An anionic polymer represented by the formula [in the general formula (III), R ₈₁ is preferably a hydrogen atom, a methyl group, an isopropyl group, an isobutyl group, a s-butyl group, a hydroxymethyl group, a hydroxyethyl group, Methylthioethyl group, mercaptomethyl group, 5-imidazolylmethyl group or 3-imidazolylmethyl group], that is, an antibacterial agent containing a polyelectrolyte complex obtained by reacting with an acidic amino acid polymer ..

The present invention also provides (1) the general formula (IV)

[0015]

[Chemical 9]

A cationic polymer represented by the formula [in the above general formula (IV), R ₉₁ is preferably a hydrogen atom, a methyl group,
Isopropyl group, isobutyl group, s-butyl group, hydroxymethyl group, hydroxyethyl group, methylthioethyl group, mercaptomethyl group, 5-imidazolylmethyl group or 3-imidazolylmethyl group], that is, a basic amino acid polymer (2 ) General formula (V)

[0017]

[Chemical 10]

An anionic polymer represented by the formula [In the general formula (V), R ₃₂ is preferably a linear or branched alkyl group having 6 to 14 carbon atoms, and a is preferably 5
0-100], that is, an antibacterial agent containing a polymer electrolyte complex obtained by reacting with an acrylic acid polymer.

The present invention also provides a cationic polymer represented by the above general formula (IV) (that is, a basic amino acid polymer).
The present invention also relates to an antibacterial agent characterized by containing a polyelectrolyte complex obtained by reacting an anionic polymer represented by the general formula (III) (that is, an acidic amino acid polymer). The present invention also provides the above general formula (I
The present invention also relates to an antibacterial agent characterized by containing a polyelectrolyte complex obtained by reacting a cationic polymer represented by V) (that is, a basic amino acid polymer) with an anionic polysaccharide. Furthermore, the present invention also relates to an antibacterial material characterized in that at least one of the above polyelectrolyte complexes is carried on a carrier.

The polyelectrolyte complex that can be used in the present invention
x: hereinafter sometimes referred to as PEC) is a substance known per se. The polyelectrolyte complex (PEC) is a solution of a cationic polymer which is a polyelectrolyte having a positive charge and an anion which is a polyelectrolyte having a negative charge, as described in, for example, JP-A-49-8581. It can be formed instantly by mixing with a solution of the polymer. The PEC thus obtained is a special ternary solvent (for example, water / acetone / of a specific composition).
It is soluble in low molecular weight salts) but insoluble in common solvents. Since the PEC membrane shows high permeability to various low molecular weight compounds, it can be used as a dialysis membrane. P
EC can provide various materials having various properties depending on the type of the starting polymer (polyelectrolyte), their mixing ratio, preparation conditions, etc., but it is conventionally known that PEC has antibacterial properties. I didn't.

In the above general formulas (I) to (V), the alkyl group having 1 to 3 carbon atoms is, for example, a methyl group, an ethyl group, or an n- or i-propyl group. The alkyl group having 1 to 4 carbon atoms has 1 to 3 carbon atoms described above.
In addition to a single alkyl group, it is, for example, an n-, i-, s-, or t-butyl group. The alkylene group having 1 or 2 carbon atoms is, for example, a methylene group, an ethylene group or an ethylidene group. The linear or branched alkylene group having 1 to 10 carbon atoms includes, for example, methylene group, ethylene group, propylene group, trimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, heptamethylene group, octamethylene group. A group, a nonamethylene group, a decamethylene group, an ethylethylene group, or an ethyltrimethylene group. The straight chain or branched chain alkyl group having 6 to 18 carbon atoms is, for example, a straight chain alkyl group having 6 to 18 carbon atoms, or 1 to 3 carbon atoms.
C6-15 alkyl group substituted with one or more straight or branched chain alkyl groups, especially
It is an alkyl group having 6 to 10 carbon atoms, which is substituted with one linear alkyl group having 1 to 3 carbon atoms. The arylene group is, for example, a phenylene group or a naphthylene group. Salts of carboxylic acid groups or sulfonic acid groups are, for example, salts with alkali metals (eg sodium, potassium) or alkaline earth metals (eg calcium, magnesium). The aryl group containing a sulfonic acid group or a salt thereof is, for example, a sulfophenyl group.

The counterions present in the starting cationic polymer and anionic polymer are the result of the reaction of the two:
It is no longer present in the PEC product. Therefore, any ion may be used as long as it does not interfere with the reaction between the two. Preferred counterions are halogen atom ions, especially chloride, bromide or iodide.

Examples of the anionic polysaccharides include hyaluronic acid, alginic acid, chondroitin sulfate A, chondroitin sulfate C, carboxymethyl cellulose, sulfated cellulose, carboxymethyl chitin, phosphorylated chitin, sulfated chitin, carboxymethyl starch, salts thereof, These include sulfonic acid compounds, carboxymethyl compounds thereof, and phosphoric acid compounds thereof.

The polyamino acids represented by the general formulas (III) and (IV) can be synthesized by a general acid anhydride monomer method, active esterification method, Maryfield method or the like.

Obtained by reacting the cationic polymer represented by the general formula (I), the general formula (II) and the general formula (IV) with the anionic polymer represented by the general formula (III) and the general formula (V). The obtained PEC has a structure in which the N ⁺ site of the cationic polymer and the acid (for example, carboxylic acid, sulfonic acid, phosphoric acid) site of the anionic polymer are sequentially bonded by Coulomb force. That is, the polymers are crosslinked by ionic bonds to form a solvent-insoluble gel.

The PEC which can be used as the antibacterial agent in the present invention may be any solvent-insoluble solid, and its average molecular weight is not particularly limited, but in general, the number of ionic seats is 10 to 10. The number of ion seats is 1,000, preferably 20 to 100. Cationic polymers represented by general formula (I), general formula (II) and general formula (IV) which are starting materials, and general formula (III) and general formula (V)
The average molecular weight of the cationic polymer represented by is also not particularly limited, but a preferable average molecular weight range is 5 to 5 for the cationic polymer represented by the general formula (I).
In the cationic polymer represented by the general formula (II), n is 10 to 1000, and in the cationic polymer represented by the general formula (IV), r is 10 to 1000. On the other hand, in the cationic polymer represented by the general formula (III), q is 10 to 1000. In the cationic polymer represented by the general formula (V), p is 10 to 1000.

Specific examples of the cationic polymer represented by the general formula (I) include quaternary polyethyleneimine chloride and poly (N, N, N ', N'-tetramethyl-alkylene-p-xylenediammonium dichloride). , Poly (N, N, N ', N'-tetramethyl-alkylene-
Diammonium dichloride), poly (N, N-dimethyl-3-hydroxypropylammonium chloride), poly (2-hydroxy-3-methacryloyloxypropyltrimethylammonium chloride), poly (2-methacryloyloxyethyltrimethylammonium chloride) , Poly (glycidyltrimethylammonium chloride), poly [(dimethyliminio) ethylene (dimethyliminio) methylene-1,4-phenylenemethylene dichloride] [generally referred to as 2X],
Poly [(dimethyliminio) hexamethylene (dimethyliminio) methylene-1,4-phenylenemethylenedichloride] [generally referred to as 6X], poly [(dimethyliminio) hexamethylene chloride] [generally,
6, 6], poly (N-ethyl-4-vinylpyridinium bromide), poly (dimethyldiallylammonium chloride), and the like.

Specific examples of the cationic polymer represented by the general formula (II) include poly (vinylbenzyltrimethylammonium chloride), polyvinylpyridinium chloride and poly (N-ethyl-4-vinylpyridinium bromide).

Specific examples of the anionic polymer represented by the general formula (III) include polyglutamic acid, polyaspartic acid or copolymers of monomers constituting these polymers, and further, these monomers and glycine, alanine, phenylalanine, It is a copolymer with tyrosine, valine, leucine, isoleucine, serine, threonine, methionine, cysteine, histidine, proline, and / or tryptophan.

Specific examples of the cationic polymer represented by the general formula (IV) include polylysine, polyarginine or copolymers of monomers constituting these polymers, and further, these monomers and glycine, alanine, phenylalanine, tyrosine, It is a copolymer with valine, leucine, isoleucine, serine, threonine, methionine, cysteine, histidine, proline, and / or tryptophan.

Specific examples of the anionic polymer represented by the general formula (V) include polyacrylic acid, polymethacrylic acid,
Polyitaconic acid monoester, polymaleic acid monoester, polyvinyl sulfonic acid, polystyrene sulfonic acid, any two or more copolymers of any of the monomers constituting these polymers, and these monomers and carboxyl groups of the monomers. 6 carbon atoms linked by an ester bond
A copolymer with a carboxylic acid derivative having -18 alkyl groups.

Specific examples of the anionic polysaccharide are as follows. (1) Hyaluronic acid and its derivatives:

[0033]

[Chemical 11]

(2) Alginic acid and its derivatives:

[0035]

[Chemical 12]

(3) Chondroitin sulfate A:

[0037]

[Chemical 13]

(4) Chondroitin sulfate C:

[0039]

[Chemical 14]

(5) Chondroitin sulfate B (dermatan sulfate) and its derivatives:

[0041]

[Chemical 15]

(6) Chondroitin sulfate D and its derivatives:

[0043]

[Chemical 16]

(7) Chondroitin sulfate E and its derivatives:

[0045]

[Chemical 17]

(8) Heparan sulfate and its derivatives:

[0047]

[Chemical 18]

(9) Heparin and its derivatives:

[0049]

[Chemical 19]

(10) κ-carrageenan and its derivatives:

[0051]

[Chemical 20]

(11) λ-carrageenan and its derivatives:

[0053]

[Chemical 21]

Even a neutral natural polysaccharide can be used as an anionic polysaccharide by subjecting it to a treatment such as carboxymethylation, sulfation or phosphorylation. For example, (12) cellulose derivative:

[0055]

[Chemical formula 22]

(13) Chitin derivative:

[0057]

[Chemical formula 23]

(14) Carboxymethyl starch and its derivatives:

[0059]

[Chemical formula 24]

(15) Amylose derivative:

[0061]

[Chemical 25]

(16) Amylopectin derivative:

[0063]

[Chemical formula 26]

(17) β-1,3′-glucan derivative (for example, curdlan):

[0065]

[Chemical 27]

(18) β-1,2'-glucan derivative:

[0067]

[Chemical 28]

(19) β-1,3'-;β-1,6'-
Glucan (eg lentinan, schizophyllan, choriolan) derivatives:

[0069]

[Chemical 29]

(20) Dextran derivative:

[0071]

[Chemical 30]

(21) Pullulan derivative:

[0073]

[Chemical 31]

(22) Agarose derivative:

[0075]

[Chemical 32]

(23) β-1,4′-galactan derivative:

[0077]

[Chemical 33]

(24) Mannan derivative:

[0079]

[Chemical 34]

(25) Inulin derivative:

[0081]

[Chemical 35]

The polymer electrolyte complex (PE used in the present invention
C) can be prepared by a usual method. That is, each aqueous solution of the above-mentioned cation polymer and anion polymer (10 ⁻⁴ / liter to 10 ⁻² mol / liter) was used to adjust the concentration ratio between the cation seat of the cation polymer and the anion seat of the anion polymer (cation seat / anion seat). Is 0.25
The reaction is carried out in an aqueous solution within the range of -4.0, preferably within the range of 0.5-2.0. The concentration ratio between the cation seat and the anion seat (cation seat / anion seat) is 0.25 to 4.
If it is out of the range of 0, it is difficult to form a polymer electrolyte complex (PEC), which is not preferable. Since this reaction is relatively active, the pH, ionic strength, temperature, etc. of the solution can be in a relatively wide range, but generally pH 3 to
9, carried out at an ionic strength of 0 to 1.0 and 20 to 40 ° C.

The charge balance of the PEC used in the present invention is
It is preferably 0 or more, more preferably 0 to +4. Here, the charge balance refers to the charge state of PEC of the cationic polymer and the anionic polymer, which are the starting materials,
It is expressed by the concentration ratio of each cation seat and anion seat. For example, when the cation seat of the cationic polymer and the anion seat of the anionic polymer used have the same concentration, the charge balance of the PEC produced is ± 0.
If the concentration ratio is higher than this (that is, the concentration at the cation seat is higher), the charge balance is positive, and if it is lower (that is, the concentration at the anion seat is higher), the charge balance is negative.
When the concentration ratio is 1.5, the charge balance is +2, and when the concentration ratio is 0.5, the charge balance is -3.3. The charge balance can be easily adjusted by changing the mixing amount of the cationic polymer aqueous solution and the anionic polymer aqueous solution having the same concentration. By adjusting the charge balance, an excess of cations or excess of anions can be obtained.

Since the polyelectrolyte complex (PEC) is obtained as a gel-like precipitate from the reaction solution, the gel-like precipitate may be used as it is, or may be directly molded and processed from the gel-like precipitate to obtain a suitable product. It can be used as an antibacterial material in a wet state or a dry state as it is in a shape (for example, a fibrous shape, a film shape, a sheet shape, a lump shape, a latex shape or a gel shape). Also, since PEC can be attached or adhered to almost any material, it can be coated on a suitable carrier to prepare an antibacterial material.

Examples of the carrier made of an organic material include:
Organic polymeric materials such as synthetic or natural resins, synthetic or natural rubber, synthetic or natural fibers, biopolymer materials, leather, wood, pulp, paper can be mentioned.

Examples of the synthetic resin include hydrocarbon polymers (for example, polyolefin, polyethylene, polypropylene, polybutene-1, poly-4-methylpentene-).
1, styrene resin, polyacetylene); halogenated hydrocarbon polymer (for example, polyvinyl chloride, polyvinylidene chloride, fluororesin); unsaturated alcohol or ether polymer (for example, polyvinyl alcohol, polyvinyl ether, polyphenylene oxide, polyphenylene sulfide) , Acetal resin, polyether, polyvinyl butyral, polyether sulfone epoxy resin); unsaturated aldehyde or ketone polymer (eg phenol resin, urea resin); unsaturated carboxylic acid polymer (eg polyacrylate, acrylic resin); Unsaturated ester polymer (eg, polyvinyl ester, polyarylate, wholly aromatic polyester, polyethylene terephthalate, polycarbonate, polybutylene diallyl phthalate, unsaturated polyester) Le resin); unsaturated nitrile polymer (e.g., polyacrylonitrile, ABS resin, AAS
Resin, AES resin); Unsaturated amine polymer (for example, polyvinylamine, polyimide, polyamide, melamine resin, polyethyleneimine, polyurethane); Others, silicone resin, the above-mentioned copolymer, blend resin, thermoplastic elastomer, etc. be able to. Examples of the natural resin include fibrin derivative resin.

Examples of the synthetic rubber include styrene-butadiene rubber, butadiene rubber, isoprene rubber, nitrilo rubber, chloroprene rubber, butyl rubber, ethylene-
Examples thereof include propylene rubber, acrylic rubber, chlorine-based polyethylene rubber, fluororubber, silicone rubber, urethane rubber, and polysulfide rubber.

Examples of the synthetic fiber include regenerated cellulose (viscose rayon, cupra) acetate, triacetate, polyamide, acrylic, vinylon, vinylidene, polyvinyl chloride, polyester, polyethylene,
Examples thereof include polypropylene, polybenzoate, polyclar, aramidphenol fiber, polyurethane fiber, fluorine fiber, polyvinyl alcohol, carbon fiber, and silicon carbide fiber. Examples of natural fibers include cotton, silk, wool, hemp, and wood.

As the carrier, an inorganic material such as glass,
Minerals (eg asbestos), enamel, cement, ceramics, artificial stones, metals (eg iron, steel, non-ferrous metals, alloys)
Can also be used. The shape and form of the carrier are not particularly limited, and may be fibrous, filamentous, film-like, sheet-like, woven, non-woven fabric, rod-like, string-like, spherical, powder, granular, porous, hollow or aggregate. Any of foam, gel, and the like may be used.

The PEC can be supported on the carrier by any known method such as coating, spraying or dipping. The PEC solution may simply be contacted with the carrier. For example, a cationic polymer aqueous solution and an anionic polymer aqueous solution are mixed in a reaction vessel, and then the reaction solution is immediately transferred to a predetermined vessel and allowed to stand for a whole day and night.
After sufficiently precipitating EC, the supernatant was removed, washed with physiological saline and distilled water about 1 to 3 times, and dried at 60 to 100 ° C. for 6 to 12 hours and annealed. It is possible to firmly attach PEC to. In order to coat the entire inner surface of the container, shake it for about one day and night to sufficiently precipitate PEC, remove the supernatant, wash as above, and anneal to firmly adhere PEC to the container surface. Can be made

In the case of fibrous, beaded or woven materials, these materials may be dipped in the PEC solution for about one day and then treated as described above. Further, as described in JP-A-50-63096, P
It is also possible to perform the EC synthesis in the presence of a water-soluble organic solvent (for example, a mixture of water, acetone and sodium bromide), and use the reaction solution as it is as a coating material for coating, spraying or dipping.

When the surface of the carrier supporting PEC is highly hydrophobic (for example, a carrier made of polycarbonate), treatment for imparting hydrophilicity to the surface (hypochlorous acid treatment, organic solvent treatment, plasma treatment, ultraviolet treatment) Etc.) is preferably performed in advance.

The PEC-supported carrier thus obtained can be used as it is as an antibacterial material, or various antibacterial products can be prepared using the antibacterial material.
As the antibacterial material that can be used as it is, a fiber material (for example, fiber, filament, woven fabric, non-woven fabric)
PEC on at least a portion (preferably the whole) of the surface of the
Loaded with, for example, gauze loaded with PEC,
Examples include absorbent cotton and fabrics (for aseptic clothing products for medical, hygiene or beauty). From these PEC-supporting fiber materials, for example, masks, eyepatches, bandages, sheets, absorbent pads (eg ear, nose, buccal or menstrual tampons), napkins can be easily prepared.

Furthermore, various aseptic clothes such as underwear (shirts, underwear, hosiery, etc.), baby linen products (for example, baby pants, bibs, baby clothes, bodice, etc.), handkerchiefs, corsets, girdles, bra,
Sea swimwear, surgical clothing, surgeon or patient aprons, life preservers, diving suits, lab clothing, protective clothing (surgical gloves), masks, surgical hats can also be prepared.

The antibacterial product prepared using the PEC-supported antibacterial material is not particularly limited as long as it is a product in which the growth of microorganisms is preferably suppressed. For example, medical equipment, hygiene equipment (for example, hospital bed covers, sheets, sterile clothes, bandages, diapers, eye gauze, tampons, contact lenses, contact lens containers, drug storage containers, blood transfusion containers), food products Related equipment (for example, food packaging materials, food storage containers), lifestyle related equipment (for example, tableware, kitchen utensils such as cupboard underlay sheets, sanitary products such as toilet seat covers), hairdressing equipment, and slime are generated. Examples of the equipment that can be easily used (for example, dialysis membrane, filtration material) and the like.

The medical devices (preferably disposable medical devices) particularly preferable as the antibacterial product prepared by using the PEC-supported antibacterial material of the present invention are listed below. Also, those preferred carrier materials are shown in parentheses.

As general medical and nursing tools, for example,
Adapter [or Connector] (Polyethylene, Polypropylene, Polyamide), Illigator (Polyvinyl chloride), Indicator (Japanese paper, Paper), Apron (Nonwoven fabric), Diaper (Polypropylene fiber, Nonwoven fabric, Paper, Cotton,
Polyamide, pulp), gauze (nonwoven fabric, paper, paper cotton, polyamide, acrylic, polyester), cup [sample holder] (polypropylene, polyethylene, polystyrene,
Paper), catheter [tube] (polyvinyl chloride, rubber, silicone, polyethylene, polypropylene, polyamide). Cover (nonwoven fabric, polyethylene), cuff (polyvinyl chloride, rubber), eye patch (gauze, nonwoven fabric, synthetic fiber), enema (synthetic fiber), cap (nonwoven fabric, paper),
Suction device (polyvinyl chloride, plastic, rubber), clamp [clip] (sponge, rubber, metal, polyamide, polyvinyl chloride, acetal resin), inspection clothing (nonwoven fabric), coil [for blood heating] (polyvinyl chloride) , Polypropylene), oxygen tent (polyethylene, polyvinyl chloride), three-way stopcock [three-way] (polyamide, polyacetal, delrin, polyvinyl chloride, polymethylpentene), artificial nose (paper, polypropylene), stopper (polyethylene, polystyrene, Polypropylene), blood transfusion set (polyethylene, polystyrene, polypropylene, rubber, polyvinyl chloride, metal), towel (nonwoven fabric), cavity mirror (polyvinyl chloride), syringe (rubber, polypropylene, medical silicone oil, polymethylpentene),
Injection needle (polyethylene, stainless steel, polypropylene, polyvinyl chloride), stethoscope (polyvinyl chloride), rectoscope (polyvinyl chloride), tape [sticking plaster]
(Acrylic, polyester, polyethylene, cotton, Japanese paper,
Polyvinyl chloride, polyamide, rayon), T-shaped belt (nonwoven fabric, paper), gloves [glove] (polyethylene, polyvinyl chloride, rubber), eyedropper (polyethylene, polypropylene), tray (compressed pulp, paper), urinal (Polyester, polyethylene, polypropylene, polyvinyl chloride,
ABS, rubber), name band (polyvinyl chloride, polyethylene), pus tray (paper, pulp), bag (polyvinyl chloride, stainless steel, polyethylene, polystyrene, rubber, paper), pad [cotton] (cotton, gauze, Polyester beads, non-woven fabric, paper), tension needle (stainless steel), splint [sine] (polyisoprene), abdominal band (spandex), cast bandage (cotton, gauze, knitted fabric, non-woven fabric, plaster, polyamide), mouthpiece (Polystyrene, paper), mask (polypropylene, polyethylene, polyamide, polyvinyl chloride, non-woven fabric), mat (polyethylene, aluminum, adhesive), manometer [pressure column] (polystyrene), cotton ball (cotton), cotton swab (white birch material) ), Finger cot (polyethylene, rubber), indwelling needle (stainless steel, poly) Vinyl, mention may be made of ABS, rubber, metal, polyethylene, polypropylene, fluorine resin), connecting tube (polyvinyl chloride, polyethylene, rubber, metal, polypropylene, polyamide) or the like.

Further, as anesthesia and operating room equipment, for example, an intrafusor for injection into a vessel (polyvinyl chloride,
ABS, polyethylene, polypropylene, rubber, metal,
Teflon), airway (polyvinyl chloride, ethylene vinyl acetate copolymer), eyelid opener (tantalum), gown (nonwoven fabric), catheter (polyvinyl chloride, silicone mixed polyvinyl chloride, latex, stainless steel, Teflon), shoes Cover (nonwoven fabric), cuff (latex), cap (nonwoven fabric, cellulose), aspirator (suction tube) (polyvinyl chloride, polyamide, polypropylene), pharyngoscope (polyvinyl chloride), connector (polyethylene), for vascular injection Set (polyethylene, polypropylene, polyacetal, Teflon, polyvinyl chloride,
Metal, silicone), towel (nonwoven fabric), counter electrode (aluminum foil, copper, stainless steel foil, bolster paper, stainless steel plate), tape (nonwoven fabric, filament), gloves (rubber, polyethylene), drape [cover cloth] ( Polyvinyl chloride, polyethylene film, non-woven fabric), drain (polyvinyl chloride, rubber, silicone rubber), biopsy needle (stainless steel, PBS,
Polyvinyl chloride, polystyrene, metal), suture (silk,
Polyamide, polypropylene, polyester, stainless steel, cut gut), mask (polyester,
Nonwoven fabric, glass fiber, polyethylene), scalpel (stainless steel, polyvinyl chloride, ABS) and the like can be mentioned.

Further, as the inspection and inspection room tools, for example, a cover glass (glass), a blood collection tube (glass, acrylic, polypropylene, natural rubber, synthetic rubber), a blood collection bottle (polypropylene, polyethylene, polystyrene), a test tube ( Polypropylene, polyethylene, styrene resin,
Glass), petri dish (polystyrene, paper, glass), Spitz tube (polypropylene, polystyrene, acetylcellulose, acrylic), dropper (polyethylene), slide glass (glass), tape (paper), electrode [for electrocardiogram, etc.] (synthetic fiber) , Paper, lead wire, polyethylene, gel), incubator (polyethylene, glass, acrylic, synthetic rubber, polystyrene), beaker (polypropylene),
Examples include pipettes (glass, polypropylene), labels (paper), and the like.

Examples of artificial organs and artificial renal chamber devices include catheters [cannula] (Teflon, silicone rubber, polyvinyl chloride, polyethylene, polypropylene, cotton), blood circuits (rubber, polyvinyl chloride, polypropylene, polyamide). , Cellulose), connector (polyamide, polyvinyl chloride, rubber, silicone, Teflon), artificial blood vessel (silicone, Dacron, Teflon), artificial lung (polycarbonate, polypropylene, polyamide, urethane foam, polyvinyl chloride), dialyze (cuprophane) , Polypropylene, polystyrene, silicone rubber, polyvinyl chloride, non-woven fabric, Japanese paper), dialysis membrane (cuprophan, polyacrylonitrile), heat exchanger (silicone rubber, stainless steel), needle (polyethylene, Ten-less steel, polyvinyl chloride, polyamide, rubber, Teflon), a filter (polycarbonate, Dacron wool, polypropylene), and the like. Also, various equipment (walls, floors, fixtures, air filters, etc.) to maintain a sterile atmosphere.
It can also be used for things that come into direct contact with the human body, such as endoscopes.

[0101]

[Function] In a cationic polyelectrolyte such as a cationic polymer, since the supported counter ion is generally a low molecular weight counter ion (for example, a halogen ion), the counter ion is desorbed from the polymer and the cation site in the polymer is removed. Is relatively easy to expose. On the other hand, in the PEC used in the present invention, since the counter ions are high-molecular compounds with each other, the 4th
The nature of quaternary ammonium exists in some neutralized form. It is surprising that the PEC having such a structure exhibits antibacterial activity, and the reason for this has not been elucidated at present, but the quaternary ammonium which is contained in the polymer body by being chemically bonded strongly is contained. It is believed that the part exhibits persistent antibacterial activity. Furthermore, in general PEC
Shows remarkably diverse properties due to changes in hydrophilic microdomain structure, surface water structure change, charge balance, etc., and therefore, in the present invention, these effects also combine to exert antibacterial properties. it is conceivable that.

[0102]

EXAMPLES The present invention will be described in more detail with reference to examples below, but these do not limit the scope of the present invention. The average molecular weight described in the following examples is the number average molecular weight measured by the vapor pressure drop method.

Example 1: PEC (2X-polyglutamine
Preparation of acid) Poly [(dimethyliminio) ethylene (dimethyliminio) methylene-1,4-phenylenemethylene dichloride] (2X), which is a cationic polymer (average molecular weight of about 6)
000) 0.015 g (0.01 mol as a cation seat) and polyglutamic acid (PG
A) (average molecular weight of about 4000) 0.013 g (0.01 mol as anion seat) were separately dissolved in 10 ml of physiological saline (pH 7.4), and thus obtained 2
Mix 5 ml of each aqueous solution at once in a beaker,
A polyelectrolyte complex gel [2X-PGA] (charge balance: ± 0) was formed. A cationic polymer aqueous solution (7 ml) prepared in the same manner as above and anionic polymer aqueous solution (3 ml) were mixed at once in a beaker to form a polymer electrolyte complex gel (charge balance: +4).

Example 2: PEC (PVBMA-aspara
Preparation of formic acid / alanine copolymer) Poly (vinylbenzyltrimethylammonium chloride) (PVBMA) (average molecular weight of about 15,000), which is a cationic polymer, 0.106 g (0.
05 mol) and aspartic acid / anionic polymer /
Random copolymer of alanine [C (Asp / Ala)]
(Aspartic acid content about 65 mol%; average molecular weight about 80
00) 0.090 g (0.05 mol as anion seat)
Are dissolved in 10 ml of distilled water (pH 9.0) separately, and 5 ml of each of the two aqueous solutions thus obtained are mixed at once at room temperature in a beaker, and a polymer electrolyte complex gel [PVBMA-C (Asp / Ala)] (charge balance: ± 0). A cationic polymer aqueous solution (7 ml) prepared in the same manner as above and anionic polymer aqueous solution (3 ml) were mixed at once in a beaker to form a polymer electrolyte complex gel (charge balance: +4).

Example 3: PEC (Polylysine-CLA)
Preparation of Cationic Polymer Poly (L-lysine) (PLL)
Random copolymer (CLA) of 1.3 mg (average molecular weight of about 3000) (0.001 mol as a cation seat) and anionic polymer acrylic acid / lauryl acrylate
(Acrylic acid content about 80 mol%; average molecular weight about 500
0) 1.8 mg (0.001 mol as anion seat) were separately dissolved in 10 ml of 0.5 mol / liter sodium chloride aqueous solution (pH 6.5), and 5 ml each of the two aqueous solutions thus obtained were dissolved. Mix at once at room temperature in a beaker, and polymer electrolyte complex gel [PLL-CL
A] (charge balance: ± 0) was formed. A cationic polymer aqueous solution (7 ml) prepared in the same manner as above and anionic polymer aqueous solution (3 ml) were mixed at once in a beaker to form a polymer electrolyte complex gel (charge balance: +4).

Example 4: PEC (lysine / serine copolymerization
Body-polyglutamic acid) Preparation of cation-polymer lysine / serine random copolymer [C (Lys / Ser)] (lysine content about 70 mol%; average molecular weight about 10,000) 0.019 g (0.01 as cation seat) Mol) and anionic polymer polyglutamic acid (PGA) (average molecular weight about 2000).
013 g (0.01 mol as anion seat) and 10 ml of physiological saline (pH 7.4) are separately dissolved,
5 ml each of the two aqueous solutions thus obtained were mixed at once in a beaker, and the polymer electrolyte complex gel [C (Lys
/ Ser) -PGA] (charge balance: ± 0). 7 ml of an aqueous cationic polymer solution prepared as described above
And 3 ml of an aqueous solution of anionic polymer were mixed at once in a beaker, and a polyelectrolyte complex gel (charge balance: +
4) was formed.

Example 5: PEC (Polylysine-Algin
Acid) Preparation Cationic polymer poly (L-lysine) (PLL)
Separately, 1.3 mg (average molecular weight of about 3000) (0.001 mol as cation seat) and 1.8 mg of anionic polymer alginic acid (Arg) (average molecular weight of about 4000) (0.001 mol as anion seat), respectively. 0.
5 mol / liter sodium chloride aqueous solution (pH 6.5)
5 ml of the two aqueous solutions thus obtained, dissolved in 10 ml
Each of them was mixed at once at room temperature in a beaker, and polymer electrolyte complex gel [PLL-Arg] (charge balance: ±
0) was formed. A cationic polymer aqueous solution (7 ml) prepared in the same manner as above and anionic polymer aqueous solution (3 ml) were mixed at once in a beaker to form a polymer electrolyte complex gel (charge balance: +4).

Example 6: PEC (lysine / serine copolymerization
Body-carboxymethyl chitin) Lysine / serine [C (Lys /
Ser)] of a random copolymer (lysine content of about 70 mol%) (average molecular weight of about 10,000) 0.019 g (0.01 mol as a cation seat) and carboxymethyl chitin (CM-Chn) (carboxy). Methylation degree about 0.65 / monosaccharide) (average molecular weight about 500)
0) 0.018 g (0.01 mol as anion seat) were separately dissolved in 10 ml of physiological saline (pH 7.4), and 5 ml of each of the two aqueous solutions thus obtained was stirred at room temperature in a beaker. To form a polymer electrolyte complex gel [C (Lys / Ser) -CM-Chn] (charge balance: ± 0). A cationic polymer aqueous solution (7 ml) prepared in the same manner as above and anionic polymer aqueous solution (3 ml) were mixed at once in a beaker to form a polymer electrolyte complex gel (charge balance: +4).

Example 7: Carrier (polyethylene chew
Fixed EXAMPLE each PEC gel 2ml prepared in 1-6 to blanking), dispensed into polyethylene tubing (inner diameter 1.0 cm), and rotated for 8 hours at 60rpm in a rotor. After coating the inner wall of the polyethylene tube with PEC, remove the supernatant, dry at 60 ° C for 4 hours, wash the inside of the tube 3 times with 10 ml of distilled water, and further dry at 80 ° C for 4 hours.
An EC-immobilized tube was obtained.

Example 8: Immobilization on carrier (gauze) Cotton gauze (10 cm × 10 cm) was immersed in each PEC gel solution prepared in Examples 1 to 8 for 8 hours. The gauze was taken out, washed with 20 ml of distilled water, dried at 60 ° C. for 4 hours, further washed with 10 ml of distilled water 3 times and dried at 80 ° C. for 4 hours to obtain a PEC-immobilized gauze.

Example 9: Carrier [contact lens material
(Polymethylmethacrylate)] To each of the PEC gel solutions prepared in Examples 1 to 6, a circular small piece (hereinafter also referred to as a circular small piece) obtained by punching out a polymethylmethacrylate plate of the same material as the contact lens into a diameter of 8 mm. It was immersed at room temperature for 10 hours. After coating with PEC, the supernatant was removed, dried at 60 ° C. for 3 hours, washed twice with 10 ml of distilled water and twice with physiological saline, and further washed with 80
It dried at 4 degreeC for 4 hours, and obtained the PEC fixed circular small piece.

Example 10: Confirmation of antibacterial properties The following microorganisms were used to investigate the antibacterial properties. Escherichia coli ATCC25932 Staphylococcus aureus ATCC25923 Serratia marcescens IFO3046 Pseudomonas aeruginosa ATCC10145

Brain Heart Infusion (BH
I) Various bacterial solutions cultured in a medium at 37 ° C. for 16 hours,
M / 15 phosphate buffer containing 0.85% sodium chloride (PBS, pH
It was diluted with 6.8) to prepare a bacterial suspension having a bacterial concentration of about 1 × 10 ⁴ cells / ml. PD medium (dipotassium phosphate 7.0 g,
2.0 g of monopotassium phosphate, 0.1 of magnesium sulfate
g, ammonium sulfate 1.0 g, sodium citrate 0.5 g, glucose 10.0 g, and bactopeptone 1
10 g (dissolved 0.0 g in 1000 ml of purified water) was added to the PEC-coated polyethylene tube prepared in Example 7, 0.1 ml of each of the above-mentioned bacterial suspensions was added and mixed, and then kept at 30 ° C. did. 30 for each tube
After culturing with shaking at 24 ° C. for 24 hours, the turbidity of the medium was visually observed to confirm the antibacterial effect. The results are shown in Table 1.

Example 11: Confirmation of antibacterial property 50 ml of PD medium was placed in a Sakaguchi flask, 3 pieces of PEC-immobilized gauze (6 cm × 6 cm) obtained in Example 8 were placed in the flask, and the same procedure as in Example 10 was performed. About 1 × 10 ⁴ cells were inoculated using 1 ml of each bacterial suspension. Similarly, an empty test flask and three pieces of gauze (6 cm × 6 cm) without PEC fixed therein were placed in the flask, and inoculated in the same manner as above was also prepared. Each flask was shake-cultured at 30 ° C. for 16 hours, and the turbidity of the medium was visually observed to confirm the antibacterial effect. The results are shown in Table 2.

Example 12: Confirmation of antibacterial property 10 ml of PD medium was placed in a sterile polyethylene tube,
2 g of the PEC-immobilized circular small pieces obtained in Example 9 were added, and 0.1 ml of each bacterial suspension as in Example 10 was added and mixed, and then the mixture was kept at 30 ° C. Similarly, a blank test tube and 2 g of a circular small piece to which PEC was not fixed were added and inoculated in the same manner as above. 30 for each tube
After culturing with shaking at 24 ° C. for 24 hours, the turbidity of the medium was visually observed to confirm the antibacterial effect. The results are shown in Table 3.

Example 13: Confirmation of persistence of antibacterial effect Purified water 1 was added to each PEC-immobilized tube prepared in Example 7.
After adding 0 ml and shaking vigorously on a shaker for 2 minutes, the washing solution was discarded. The same washing operation was further performed 4 times (5 times in total), and each tube was dried at 60 ° C. for 2 hours. Using the tube thus pretreated, the persistence of the antibacterial effect was examined by the same procedure as in Example 10 using Escherichia coli (ATCC25932). The results are shown in Table 4.

Example 14: Confirmation of persistence of antibacterial effect 1000 ml of each PEC-immobilized gauze prepared in Example 8
In a beaker of No. 3, 500 ml of purified water was added, the mixture was stirred for 5 minutes using a magnetic stirrer, and then the washing solution was discarded. The same washing operation was further performed 4 times (5 times in total), each gauze was taken out, and dried at 60 ° C. for 4 hours. Using the gauze thus pretreated, the persistence of the antibacterial effect was examined by the same procedure as in Example 11 using Escherichia coli (ATCC25932).
The results are shown in Table 5.

Example 15: Confirmation of persistence of antibacterial effect Each PEC-immobilized circular piece prepared in Example 9 was placed in a sterile polyethylene tube, 10 ml of purified water was added, and the mixture was shaken vigorously for 2 minutes on a shaker. The wash solution was discarded. The same washing operation was further performed 4 times (5 times in total), the circular small pieces were taken out, and dried at 60 ° C. for 4 hours. Using the circular pieces thus pretreated, the persistence of the antibacterial effect was examined by the same procedure as in Example 12 using Escherichia coli (ATCC25932). The results are shown in Table 6.

Example 16: Confirmation of antibacterial property Filter paper (TOYO, No. 5B) was immersed in each of the PEC gel solutions prepared in Examples 1 to 8 for 8 hours. The filter paper was taken out, washed with 20 ml of distilled water, dried at 60 ° C. for 4 hours, further washed with 10 ml of distilled water 3 times, and dried at 80 ° C. for 4 hours. The obtained filter paper was cut out into a disk shape having a diameter of 13 mm and subjected to gas sterilization treatment to obtain a disk for antibacterial effect test described below. On the other hand, a similar disc-shaped filter paper that was not immersed in the PEC gel solution was similarly gas-sterilized to give a control disk.

The four kinds of bacteria described in Example 10 were used in Example 1
In the same manner as in 0, the cells were cultivated with shaking in BHI medium overnight,
After centrifuging three times with the medium, it was similarly diluted with BHI medium to prepare a bacterial suspension having a bacterial concentration of about 1 × 10 ⁷ cells / ml.
20 μl of this bacterial suspension was inoculated on the disc for antibacterial effect test and the disc for control, left at 37 ° C. for 2 hours, and then placed on a tryptosome agar plate so that the disc inoculated surface and the agar plate were in contact with each other, and 37 Each disc was removed after standing at 0 ° C. for 1 hour. Furthermore, after culturing at 37 ° C. for 24 hours, the formation of colonies appearing on the plate was observed. The results are shown in Table 7.

In Tables 1 to 6 below, the symbols have the following meanings. ++: Strong turbidity, ++: Turbidity, +: Some turbidity, ±: No change, −: Transparent.

In Table 7 below, the symbols indicate the degree of colony formation, and the symbols have the following meanings. ++: Large ++: Medium +: Small ±: Very small −: No change

[0123]

Since the antibacterial agent of the present invention is generally insoluble in a solvent, it can be used in a wide variety of applications. In addition, the antibacterial activity can be maintained for a long period of time. Furthermore,
Various antibacterial agents having different antibacterial strengths can be easily provided.

[0124]

[Table 1]

[0125]

[Table 2]

[0126]

[Table 3]

[0127]

[Table 4]

[0128]

[Table 5]

[0129]

[Table 6]

[0130]

[Table 7]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display area A01N 43/60 8930-4H // C08G 81/00 NUT 7142-4J (72) Inventor Masaharu Akimoto Tokyo 1-11-4 Higashi-Kanda, Chiyoda-ku, Tokyo Stock Company

Claims (5)

[Claims] 1. A compound represented by the general formula (I): Or a cationic polymer represented by the general formula (II): And a cationic polymer represented by the general formula (III): An antibacterial agent comprising a polyelectrolyte complex obtained by reacting with an anionic polymer represented by. 2. A compound represented by the general formula (IV): And a cationic polymer represented by the general formula (V): An antibacterial agent comprising a polyelectrolyte complex obtained by reacting with an anionic polymer represented by. 3. A polyelectrolyte complex obtained by reacting the cationic polymer represented by the general formula (IV) according to claim 2 with the anionic polymer represented by the general formula (III) according to claim 1. An antibacterial agent comprising: 4. An antibacterial agent comprising a polyelectrolyte complex obtained by reacting a cationic polymer represented by the general formula (IV) according to claim 2 with an anionic polysaccharide. 5. An antibacterial material comprising at least one polymer electrolyte complex according to any one of claims 1 to 4 supported on a carrier.