JP6081156B2 - Hydrogel - Google Patents

Description

  The present invention relates to a hydrogel. More specifically, the present invention relates to a hydrogel having an antibacterial function and used for skin and wounds.

Hydrogel is known as a material that has a high affinity for water and absorbs moisture well, is excellent in adaptability and adhesion to a living body, and can impart a cool feeling.
Because of these characteristics, hydrogels are widely studied for use in living bodies such as medical care, cosmetics, and health care. In particular, many properties can be effectively utilized for the development of wound dressings in medicine. Hydrogel has good adhesion to the wound, quickly absorbs and retains exudate from the wound, promotes wound healing by keeping the wound in a moist environment, and further relieves pain by imparting a cool feeling Can do. In addition, hydrogel is excellent in wound observability due to its transparency, and due to its flexibility and adaptability, it does not feel uncomfortable at the time of application, does not damage the new tissue at the time of peeling, and can reduce the peeling stimulus.

  Due to the increase in lifestyle-related diseases and aging in recent years, diabetic, venous or arterial leg ulcers and extremely incurable wounds such as pressure ulcers are increasing, and it is difficult to treat them. Patients with such chronic wounds often have poor nutritional status and blood circulation, and skin tissue is also fragile, so the risk of skin damage due to exudate and infection by bacteria is very high. Once skin injury or wound infection occurs, the condition deteriorates all at once and healing is delayed. In the case of a lower leg ulcer, the lower limb may have to be cut. For such chronic wounds, wound management using a wound dressing utilizing the properties of hydrogel is effective.

For example, Patent Document 1 discloses a method for producing a PVA hydrogel by irradiating a prehydrogel produced from an aqueous polyvinyl alcohol solution with respect to a method for producing a polyvinyl alcohol (PVA) hydrogel that can be used as a wound dressing. Is described.
Patent Document 2 proposes “a wound dressing using a hydrogel composed of a water-soluble polymer, a saccharide, and water”. And in this patent document 2, the metal salt of the sugar acid containing silver which has bactericidal action as saccharides is illustrated.

Japanese Patent Laid-Open No. 9-263671 JP-A-10-28726

  As described above, various studies have been made on hydrogels so that they can be suitably used for living organisms, and in the use of wound dressing materials and the like, antibacterial agents have been included to prevent infection. Yes. However, antibacterial agents contained in hydrogels act not only on the causative bacteria of infection but also on normal cells in the healing process, and rather delay healing for incurable wounds such as chronic wounds. There was also a risk of letting it go.

  Therefore, the main object of the present invention is to provide a hydrogel that has a long-lasting antibacterial action, has little irritation to normal tissues, and has high biocompatibility.

  In order to solve the above-mentioned problems, the present inventors have intensively studied the hydrogel structure, the type of antibacterial agent, and the behavior of the antibacterial agent in the hydrogel. As a result, the present inventors have completed the present invention.

That is, the present invention provides a hydrogel that includes a hydrophilic polymer, water, and a quaternary ammonium salt compound and is crosslinked by irradiation with radiation.
In this hydrogel, the quaternary ammonium salt compound is preferably a cetylpyridinium salt.
The hydrogel of the present invention comprises 7 to 40% by mass of one or more selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidone, and carboxymethyl cellulose / sodium as a hydrophilic polymer, and 59 to 92% by mass of water. The quaternary ammonium salt compound preferably contains 0.03 to 1% by mass of cetylpyridinium chloride.
Moreover, when adding three of polyvinyl alcohol, polyvinylpyrrolidone, and carboxymethylcellulose sodium as hydrophilic polymer, each content mass ratio of polyvinyl alcohol: polyvinylpyrrolidone: carboxymethylcellulose sodium is 97-50: It is preferable that it is 2-49: 0.2-20. As described above, when the cetylpyridinium salt is contained in a hydrogel containing a specific hydrophilic polymer, a hydrogel having a continuous antibacterial action and less irritating to normal tissues can be obtained.
The present invention also provides a hydrogel comprising a hydrophilic polymer, water, and a quaternary ammonium salt and having an IC ₅₀ value of 20% or more.

  According to the present invention, it is possible to provide a hydrogel that has a long-lasting antibacterial action, has little irritation to normal tissues, and has high biocompatibility.

  Hereinafter, preferred embodiments for carrying out the present invention will be described. In addition, embodiment described below shows an example of typical embodiment of this invention, and, thereby, the range of this invention is not interpreted narrowly.

  The hydrogel according to the present invention contains at least a hydrophilic polymer, water, and a quaternary ammonium salt compound, and is crosslinked by irradiation.

The hydrophilic polymer used for constituting the hydrogel according to the present invention is not particularly limited as long as it contains at least one kind of polymer that can be crosslinked by irradiation with radiation to form a gel.
Examples of hydrophilic polymers that are cross-linked by irradiation with radiation include polyvinyl alcohol, polyvinyl pyrrolidone, carboxymethylcellulose, sodium carboxymethylcellulose, polyacrylamide, polyacryloylmorpholine, water-soluble polyvinyl acetal, poly-N-vinylacetamide, hydroxyethylcellulose, hydroxy Examples include propylcellulose, methylcellulose, hydroxypropylmethylcellulose, hydroxyethylmethylcellulose, gelatin, and casein, and derivatives thereof. Examples of these hydrophilic polymer derivatives include derivatives in which various monomers are copolymerized or graft-polymerized, and hydroxyl groups, amino groups, amide groups, and carboxyl groups possessed by resins such as etherification, esterification, and amidation. And derivatives obtained by acetalization, derivatives partially crosslinked with a crosslinking agent, and the like. In particular, the hydrophilic polymer that is cross-linked by irradiation with radiation is more preferably polyvinyl alcohol, polyvinyl pyrrolidone, or carboxymethyl cellulose / sodium.

Further, in order to improve the water absorption of the leachate, the adhesion to the living body, etc., a hydrophilic polymer other than the hydrophilic polymer may be added. For example, the following synthetic, semi-synthetic, or natural polymers may be added. Various hydrophilic polymers can be used.
Although it does not specifically limit as a synthetic hydrophilic polymer, For example, vinyl polymer (for example, polyvinyl methyl ether, carboxy vinyl polymer, etc.), acrylic polymer (for example, sodium polyacrylate, etc.), polyethyleneimine, and Polyethylene oxide or the like can be used.

  Although it does not specifically limit as a semisynthetic hydrophilic polymer, For example, starch type polymer (for example, carboxymethyl starch, methylhydroxypropyl starch, etc.), cellulosic polymer (for example, ethyl cellulose, cellulose sodium sulfate, etc.), And alginic acid polymers (for example, sodium alginate, propylene glycol alginate, etc.) and the like can be used.

Although it does not specifically limit as a natural hydrophilic high molecular compound, For example, a plant polymer, a microbial polymer, an animal polymer, etc. can be used.
Specific examples of the plant polymer include gum arabic, gum tragacanth, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, and starch (eg, rice, corn, potato, and wheat starch). .
Specific examples of the microbial polymer include xanthan gum, dextrin, dextran, succinoglucan, and pullulan.
Specific examples of the animal polymer include albumin.

Each of the hydrophilic polymers may be used singly or in combination of two or more, and even a copolymer having two or more skeletons is used in a mixture containing two or more. May be.
Among the above hydrophilic polymers, polyvinyl alcohol (hereinafter sometimes abbreviated as “PVA”), polyvinyl pyrrolidone (hereinafter sometimes abbreviated as “PVP”), and carboxymethylcellulose sodium ( Hereinafter, it may be abbreviated as “CMC · Na”.) It is preferable to use one or more selected from the group consisting of: Of these hydrophilic polymers, PVA and / or PVP are preferably used, and a combination of PVA, PVP and CMC · Na is more preferably used. By using these hydrophilic polymers, it is possible to easily form a hydrogel that is cross-linked with each other by irradiation with radiation and excellent in moisture absorption and water retention. Moreover, the hydrogel excellent in affinity with the quaternary ammonium salt type compound (hence, cetyl pyridinium salts, such as cetyl pyridinium chloride) mentioned later can be obtained.

When PVA is used as the hydrophilic polymer, the degree of polymerization of PVA measured according to JIS K6726 is not particularly limited, but is preferably 300 to 5000, and more preferably 1000 to 4000. Moreover, although the saponification degree of PVA (mol% of the vinyl alcohol unit of PVA) measured according to JISK6726 is not specifically limited, For example, 60-100 are suitable and 80-100 are more suitable.
When the polymerization degree and the saponification degree of PVA are in the above ranges, it is possible to easily form a hydrogel that has good water absorbability and easily retains water.

The content of the hydrophilic polymer in the hydrogel is not particularly limited, but is preferably 5 to 60% by mass, more preferably 7 to 40% by mass, based on the total mass of the hydrogel raw material, More preferably, it is 10-30 mass%.
When the content of the hydrophilic polymer is within the above range, it is possible to easily form a hydrogel having high cohesion and good moisture absorption.

When the hydrogel according to the present invention contains PVA and PVP as hydrophilic polymers, the mass ratio of PVA: PVP is preferably 97 to 50: 3 to 50 in the total mass of the raw material of the hydrogel, More preferably, it is 95-80: 5-20.
In addition, when the hydrogel according to the present invention contains PVA, PVP and CMC · Na as hydrophilic polymers, the mass ratio of PVA: PVP: CMC · Na is preferably in the total mass of the hydrogel raw material. It is 97-50: 2-49: 0.2-20, More preferably, it is 95-80: 4-19: 0.5-10.

The radiation that causes mutual crosslinking of the hydrophilic polymer is not particularly limited, and examples thereof include α rays, β rays, γ rays, X rays, electron beams, visible rays, ultraviolet rays, and infrared rays. Of these radiations, γ-rays, X-rays, electron beams, visible rays, and ultraviolet rays are preferably used, and the dose can be easily controlled and sterilized at the same time. A wire or an electron beam is more preferable.
Since the hydrophilic polymer used in the hydrogel of the present invention is cross-linked with each other by irradiation with the radiation, it can form a gel without using a separate cross-linking agent. Therefore, safety can be improved by using a hydrogel that does not contain a crosslinking agent.

The irradiation amount of the radiation when forming the hydrogel is not particularly limited as long as a crosslinking reaction occurs.
For example, when γ-ray, X-ray, electron beam, etc. are irradiated to cause a crosslinking reaction, the composition before forming the hydrogel (hereinafter also referred to as “hydrogel composition”) is irradiated. The integrated irradiation dose can usually be in the range of 0.1 to 1000 kGy, preferably 1 to 100 kGy. By setting the integrated irradiation amount within the above range, the crosslinking reaction can be controlled to such an extent that it has an appropriate cohesive force (gel strength) and moisture absorption.
Therefore, it is preferable that the cumulative dose of radiation is appropriately set according to the type of raw material used, such as a hydrophilic polymer, so that a hydrogel having good cohesive force and water absorbability can be formed.

  The hydrogel according to the present invention encloses water by a network structure of hydrophilic polymers cross-linked with each other. Although content of the water in the said hydrogel is not specifically limited, It is preferable that it is 40-95 mass%, It is more preferable that it is 59-92 mass%, It is further more preferable that it is 69-89 mass%. .

The quaternary ammonium salt compound contained in the hydrogel according to the present invention imparts an antibacterial function to the hydrogel.
In the present invention, the “quaternary ammonium salt compound” means “a quaternary ammonium salt in which four alkyl groups or aryl groups are bonded to a nitrogen atom” (hereinafter simply referred to as “quaternary ammonium salt”). And a “pyridinium salt-based compound”.
Examples of the anion that ion-bonds with the quaternary ammonium type cation in the “quaternary ammonium salt compound” include chloride ion, bromide ion, fluoride ion, and iodide ion. Ions and bromide ions are preferred.

  Specific examples of the “quaternary ammonium salt” include benzalkonium chloride, benzyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, benzethonium chloride, methylbenzethonium chloride, hexadecyltrimethylammonium bromide (cetrimonium bromide), Examples include tetraethylammonium bromide and didecyldimethylammonium chloride.

  Specific examples of the “pyridinium salt-based compound” include alkylpyridinium salts such as cetylpyridinium chloride and cetylpyridinium bromide.

  The quaternary ammonium salt compounds (quaternary ammonium salts and pyridinium salt compounds) may be used singly or in combination of two or more, and a mixture containing two or more is used. May be.

As the “quaternary ammonium salt compound”, the above “pyridinium salt compound” is preferably used, and among the “pyridinium salt compounds”, a cetylpyridinium salt is more preferably used, and cetylpyridinium chloride is used. More preferably, it is used.
By containing a cetylpyridinium salt such as cetylpyridinium chloride, the hydrogel can impart excellent antibacterial properties to the hydrogel and make it difficult to elute (slow release) the cetylpyridinium salt from the hydrogel. Can do. Therefore, it is possible to obtain a hydrogel that easily retains the cetylpyridinium salt in the hydrogel and easily maintains antibacterial properties.

One of the factors that make alkylpyridinium salts such as cetylpyridinium salts difficult to elute from the hydrogel (sustained release) is that the alkyl group of the alkylpyridinium salt (hexadecyl (cetyl) group in the case of cetylpyridinium chloride) is a hydrophilic polymer. It is considered that the molecular chain is bound to or entangled with the molecular chain, and as a result, the alkylpyridinium salt is considered to be difficult to elute (sustained release) from the hydrogel. From this inference, it is considered suitable to use one or more selected from the group consisting of PVA, PVP, and CMC · Na as the hydrophilic polymer.
In addition, as one of the above factors, when a salt such as CMC · Na is contained as a hydrophilic polymer, sodium ions (Na ⁺ ) of CMC · Na are liberated in hydrogel or in water, and alkyl such as cetylpyridinium chloride. It is considered that the anion of pyridinium salt (in the case of cetylpyridinium chloride, chloride ion; Cl ⁻ ) is released, and the anion derived from CMC · Na and the cation derived from cetylpyridinium chloride are ionically bonded. As a result, the alkylpyridinium salt Is considered to be difficult to elute (sustained release) from the hydrogel. From this reasoning, it is considered preferable to use a hydrophilic polymer that forms a salt such as CMC / Na.

  When a cetylpyridinium salt such as cetylpyridinium chloride is used as the “quaternary ammonium salt compound”, the content of the cetylpyridinium salt in the total hydrogel mass is preferably 0.01 to 3% by mass. 03-1 mass% is more preferable, and 0.05-0.5 mass% is still more preferable. When the content of the cetylpyridinium salt such as cetylpyridinium chloride is within the above range, the antibacterial properties of the hydrogel can be enhanced.

The hydrogel according to the present invention preferably has antibacterial properties and has a low sustained release property of the added quaternary ammonium salt compound. “Having antibacterial properties” for the hydrogel means that, for example, in the test for confirming the number of bacteria such as an antibacterial test described later, the hydrogel reduces or does not grow the bacteria used in the test.
In addition, “low sustained release” for the hydrogel means that, for example, in the sustained release test described later, the sustained release rate is low, and preferably the sustained release rate is less than 20%. More preferably, the sustained release rate of the hydrogel is less than 10%. The sustained release rate of the hydrogel is within this range, so that it is possible to exert a continuous antibacterial action at a predetermined site coated with the hydrogel and to suppress irritation and damage to normal tissues and cells. it can.

  A preferred composition of the hydrogel according to the present invention is 7 to 40% by mass, 59 to 92% by mass of water, cetylpyridinium chloride, 0.1 to 2% or more selected from the group consisting of PVA, PVP, and CMC · Na. The content ratio of PVA: PVP: CMC.Na is 97-50: 2-49: 0.2-20. A more preferred composition of the hydrogel according to the present invention is 10 to 30% by mass of one or more selected from the group consisting of PVA, PVP, and CMC.Na, 69 to 89% by mass of water, cetylpyridinium chloride 0 0.05 to 0.5 mass%, and the mass ratio of PVA: PVP: CMC · Na is 95 to 80: 4 to 19: 0.5 to 10.

  In the halo test defined in JIS L1902, the hydrogel according to the present invention preferably has a circular growth inhibition zone (halo) of 3 mm or less in width, more preferably 2 mm or less in width. More preferably, no stop band is formed. By controlling the elution (sustained release) of the quaternary ammonium salt compound in the hydrogel, the growth inhibition zone in the halo test is not formed, or even if it is formed, it is considered to be 3 mm or less. It is thought that it can reduce the effects and adverse effects on neoplastic cells and tissues

The hydrogel of the present invention preferably has an IC ₅₀ value (50% inhibitory concentration) of 20% or more, more preferably 30% or more, and further preferably 50% or more according to a measurement method described later. . The IC ₅₀ value is a test solution concentration that inhibits the number of colonies of a predetermined cell to be cultured by 50%. The smaller the value, the greater the toxicity to the living body, and the larger the value, the less toxic and the higher the safety. .
The hydrogel of the present invention uses the aforementioned predetermined hydrophilic polymer and quaternary ammonium salt compound and causes a cross-linking reaction by radiation irradiation, so that it has a high IC ₅₀ value, and stimulates living organisms and cells. It is considered that a hydrogel with low toxicity can be realized.
In addition, as long as the hydrogel has an IC ₅₀ value of 20% or more, more preferably 30% or more, the above-described hydrophilic polymer and quaternary ammonium salt compound can be used. The crosslinking reaction may not be caused by irradiation.

  In addition, the hydrogel according to the present invention may contain antibacterial agents, antiseptics, antioxidants, antifoaming agents, stabilizers, surfactants, crosslinking agents other than the “quaternary ammonium salt-based compounds” as necessary. , Plasticizers, tackifiers, viscosity modifiers, colorants, medicinal ingredients, and the like.

  The hydrogel according to the present invention comprises a preparation step for preparing a liquid hydrogel composition containing a hydrophilic polymer, water, and a quaternary ammonium salt compound, and the hydrogel composition is cured. It can manufacture by performing a shaping | molding process.

In the preparation step, a mixing step is performed in which a hydrophilic polymer and a quaternary ammonium salt compound are mixed with water to obtain the hydrogel composition. The mass ratio of each component in a mixing process can be mixed in the preferable range mentioned above, for example.
In the mixing step, from the viewpoint of solubility in water, it is preferable to first add a hydrophilic polymer to water and dissolve it, and then add a quaternary ammonium salt.
In the mixing step, the hydrogel composition may be stirred under conditions such as heating and reduced pressure as necessary.

Next, the hydrogel composition that has undergone the mixing process is irradiated with radiation to perform a molding process for curing the hydrogel composition. Irradiation with radiation can be performed, for example, with the type of radiation and the irradiation dose described above.
Further, in the molding step, for example, a sheet-like base material, a package, a molding die, etc. are hydrolyzed so that the hydrogel composition can be easily irradiated with radiation or the hydrogel composition can be easily cured. It is preferable to place, contain or fill the gel composition.
The method of irradiating with the hydrogel composition placed on the sheet-like substrate is suitable for producing a hydrogel integrated with the sheet-like substrate.
A method of performing radiation irradiation in a state where the hydrogel composition is contained or filled in a package or a mold is suitable for forming a thick hydrogel.
In the case of this method, the package is preferably one that transmits radiation, and one that has been sterilized is preferably used. Moreover, in order to obtain a flat sheet-like hydrogel, it is preferable to perform radiation irradiation in a state in which a package enclosing the hydrogel composition is sandwiched between restraining plates (for example, stainless steel plates).

The main effects produced by the hydrogel according to this embodiment will be described.
As described above, the hydrogel according to the present embodiment can be excellent in cohesive force and moisture absorption.
In addition, the hydrogel according to the present embodiment has antibacterial properties and can maintain antibacterial properties because the quaternary ammonium salt compounds in the hydrogel are difficult to elute (slow release) from the hydrogel. Therefore, it is possible to exert a concentrated and continuous antibacterial action at the location where the hydrogel is provided, and to suppress irritation and damage to normal tissues and cells.
Therefore, if this hydrogel is used as a wound dressing, it can effectively absorb moisture such as sweat and exudate, create a moist environment suitable for wound healing, and shorten the wound healing period. There is also a possibility.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to these.

<Example 1>
In the flask, 400 parts by mass of water, 90 parts by mass of PVA (trade name “JP-18” (polymerization degree 1800, degree of saponification 87.0 to 89.0) manufactured by Nippon Vinegar Poval Co., Ltd.), PVP ( 10 parts by mass of BASF Japan Co., Ltd. trade name “Lubiscol K90” and 2.5 parts by mass of CMC · Na (Nippon Paper Chemical Co., Ltd. trade name “Sunrose F30MC”) are added at 80 ° C. The mixture 1 was prepared by stirring for about 20 minutes while heating.
Thereafter, 0.4 parts by mass of cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the mixed solution 1 and stirred for about 10 minutes while heating at 80 ° C. to prepare a composition for hydrogel.

The obtained composition for hydrogel was enclosed in a sterile packaging material made of PET.
Next, in order to form a flat sheet-like hydrogel, a sterilized packaging material in which the hydrogel composition was sealed was sandwiched between stainless plates to hold the shape. In this state, an electron beam irradiation apparatus is used to irradiate the composition for hydrogel with an electron beam under the condition of an integrated irradiation amount of 50 kGy, and the composition is cured to form a sheet-like hydrogel having a thickness of 1 mm. A gel was produced.

<Examples 2 to 4>
The content of cetylpyridinium chloride in the hydrogel composition of Example 1 was changed to 0.8 parts by mass for Example 2, 1.0 part by mass for Example 3, and 1.2 parts by mass for Example 4. A hydrogel was produced in the same manner as in Example 1 except that.

<Examples 5 and 6>
0.4 parts by mass of cetylpyridinium chloride in the hydrogel composition of Example 1, Example 5 is 0.4 parts by mass of benzalkonium chloride (hereinafter abbreviated as “BKC”), and Example 6 is benzyltrimethyl chloride. The hydrogels of Examples 5 and 6 were produced in the same manner as in Example 1 except that ammonium was changed to 0.4 part by mass (hereinafter abbreviated as “BTMAC”).

<Comparative Examples 1 and 2>
Except for 0.4 parts by mass of cetylpyridinium chloride in the hydrogel composition of Example 1, Comparative Example 1 was 0.5 parts by mass of polyhexamethylene biguanide, and Comparative Example 2 was 1.0 parts by mass of polyhexamethylene biguanide. Produced a hydrogel in the same manner as in Example 1.

  The following evaluation was performed about the manufactured hydrogel of the Example and the comparative example.

<Antimicrobial test>
The test method of the antibacterial test in the present invention is shown below.
Place the sterilized general agar medium in a sterile petri dish.
Separately, a 1 mL solution of cultured Staphylococcus aureus (ATCC 12973) (number of initial bacteria: 6.3 × 10 ⁶ CFU / mL) is dropped on a general agar medium, and the whole medium is extended.
This allows bacteria to spread over the surface of the medium.
After confirming that the bacteria have been absorbed on the surface of the agar medium, a hydrogel test specimen cut into a circle having a diameter of 20 mm is placed on the agar medium containing bacteria.
After standing at 37 ° C. for 18 hours, the hydrogel is removed, and only the agar portion that has been in contact with the hydrogel is removed.
Dilute at 1 times with sterilized distilled water, and calculate the number of bacteria in the diluted solution.

<Slow release rate>
The method of using cetylpyridinium chloride as a method for the sustained release test of the quaternary ammonium salt compound in the present invention is shown below.
A hydrogel whose mass has been measured in advance is placed in a polystyrene vial, and then 20 mL of a 0.9% sodium chloride aqueous solution (hereinafter referred to as physiological saline) is added and heated at 37 ° C.
Six hours later, the whole amount of the physiological saline is collected, passed through a filter having a pore size of 0.45 μm, put into a quartz cell having an optical path length of 10 mm, and a UV spectrum is measured in a wavelength range of 200 to 400 nm using a spectrophotometer.
In addition, since components, such as a hydrophilic polymer, elute from hydrogel and may influence UV absorption, the hydrogel which does not contain a cetyl pyridinium chloride is prepared separately, and is used as a blank.
In order to calculate the sustained release rate, cetylpyridinium chloride is dissolved in physiological saline to a concentration of 0.39 to 50 μg / mL, and used as a standard sample for a calibration curve. Absorption at a wavelength of 260 nm derived from the pyridinium ring of cetylpyridinium chloride is applied to the above calibration curve and calculated as a sustained release rate (%).
This operation is similarly performed after 72 hours and 72 hours after immersion of the hydrogel in physiological saline.

<Hello test>
The test method of the halo test in the present invention is shown below.
Place the sterilized general agar medium in a sterile petri dish.
Separately, a 1 mL solution of cultured Staphylococcus aureus (ATCC 12973) (number of initial bacteria: 6.3 × 10 ⁶ CFU / mL) is dropped on a general agar medium and spread over the whole medium. This allows bacteria to spread over the surface of the medium.
After confirming that the bacteria have been absorbed on the surface of the agar medium, a hydrogel test specimen cut into a circle having a diameter of 20 mm is placed on the agar medium containing bacteria.
After standing at 37 ° C. for 18 hours, the agar medium on which the hydrogel is allowed to stand is photographed, and the length of the growth inhibition circle is measured using analysis software (Winroof).

<IC ₅₀ value>
(1) Preparation of test solution The IC ₅₀ value in the present invention is based on ISO10993 and is measured by the following measuring method.
A 1 g hydrogel test piece is cut, cut into as small pieces as possible, and placed in a polystyrene container.
10 mL of medium M05 is added thereto, and then left to stand at 37 ° C. for 24 hours in a carbon dioxide incubator.
The extract extracted from this was used as a 100% test solution, and this 100% test solution was further diluted with M05 medium to prepare test solutions having concentrations of 50%, 25%, 12.5%, and 6.25%. .
(2) Cell Line Culture After cell isolation of V79 of the cell line by trypsinization, the cells are seeded in a 24-well microplate so that the number of appearing colonies is 50 cells or more. The plate is allowed to stand for 15 hours to allow the cells to adhere.
Discard the medium from the 24-well microplate, add 1 mL of the test solution of each concentration described above, and incubate at 37 ° C. for 6 days.
After completion of the culture, washing and fixing with methanol, Giemsa staining solution is added to stain the colony. The number of colonies is counted with a stereomicroscope.
(3) Calculation of IC ₅₀ value As a control group (the number of colonies: 100%) cultured in M05 medium without adding a test solution, the number of colonies formed after addition of the test solution at each concentration was counted, The colony formation rate is calculated by the following formula.
Colony formation rate (%) = (number of colonies after addition of test solution of each concentration / number of control colonies) × 100
From the relationship of the colony formation rate at each test solution concentration calculated from the above equation, the test solution concentration (%) with a colony formation rate of 50% is determined, and this value is taken as the IC ₅₀ value (%). That is, the test solution concentration (%) that inhibits the number of control colonies by 50% is taken as the IC ₅₀ value.

The compounding ratio and evaluation result of each hydrogel of Examples 1-6 and Comparative Examples 1-2 are shown in Tables 1-3. In addition, the ellipsis of the compound in Tables 1-3 is as follows.
PVA: polyvinyl alcohol PVP: polyvinyl pyrrolidone CMC / Na: carboxymethyl cellulose / sodium CPC: cetylpyridinium chloride BKC: benzalkonium chloride BTMAC: benzyltrimethylammonium chloride PHMB: polyhexamethylene biguanide

The hydrogels of Examples 1 to 4 had an IC ₅₀ value of 20% or more, the number of bacteria in the agar decreased, and no growth inhibition zone was formed. From these results, the hydrogels of Examples 1 to 4 have excellent antibacterial properties and almost no sustained release, can exert a continuous antibacterial action, and stimulate and damage normal tissues and cells. It is thought that it can be suppressed.
It was confirmed that the hydrogels of Examples 5 and 6 have antibacterial properties because IC ₅₀ values were 20% or more and the number of bacteria in the agar decreased. In addition, the hydrogel of Example 5 had a growth inhibition zone width of 2.7 mm and had a sustained release property compared to the hydrogels of Examples 1 to 4, but Comparative Example 1 It was confirmed that the sustained release property was low as compared with the hydrogel of ~ 2.
Although the hydrogels of Comparative Examples 1 and 2 have antibacterial properties, they are easy to elute (sustained release) PHMB in the hydrogel and have a low IC ₅₀ value. And not enough in terms of stimulation to normal tissues and cells.

  The hydrogel according to the present invention is, for example, a wound dressing material to be affixed to a living body, a surgical tape, a fixation tape for insertion portions such as catheters and infusion tubes and a line portion, an adhesive material for fixation such as an electrocardiogram electrode and a magnetic therapy device It is preferably used as an adhesive material for stoma devices, a poultice material, and an adhesive material for skin care or beauty.

Claims (4)

A hydrophilic polymer, water, and a quaternary ammonium salt compound,
The hydrophilic polymer consists of polyvinyl alcohol, polyvinyl pyrrolidone, and carboxymethylcellulose sodium,
The mass ratio of polyvinyl alcohol: polyvinylpyrrolidone: carboxymethylcellulose / sodium is 97-50: 2-49: 0.2-20,
Low-elution hydrogel cross-linked by irradiation. A hydrophilic polymer, water, and a quaternary ammonium salt compound,
The hydrophilic polymer is composed of polyvinyl alcohol, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose,
The content mass ratio of polyvinyl alcohol: polyvinylpyrrolidone: carboxymethylcellulose sodium is 95-80: 4-19: 0.5-10,
Low-elution hydrogel cross-linked by irradiation. The low-eluting hydrogel according to claim 1 or 2, wherein the quaternary ammonium salt compound is a cetylpyridinium salt. The hydrophilic polymer of 7 to 40% by mass, the water of 59 to 92% by mass, and cetylpyridinium chloride 0.03 to 1% by mass as the quaternary ammonium salt compound, The low-eluting hydrogel according to any one of the above.